Phenotypes associated with this allele

• Allele Symbol: Tg(Myh6-cre)2182Mds
• Allele Name: transgene insertion 2182, Michael D Schneider
• Allele ID: MGI:2386742
• Summary: 118 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ctnnb1^tm2(Nfkbia)Rsu/Ctnnb1^+ Tg(Myh6-cre)2182Mds/0	B6.Cg-Ctnnb1^tm2(Nfkbia)Rsu Tg(Myh6-cre)2182Mds	MGI:3706583
cn2	Gt(ROSA)26Sor^tm3(CAG-EYFP)Hze/Gt(ROSA)26Sor^+ Hira^tm1c(EUCOMM)Wtsi/Hira^tm1d(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds/0	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-EYFP)Hze Hira^tm1c(EUCOMM)Wtsi/Hira^tm1d(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds	MGI:5823159
cn3	Smarcd3^tm1.1Bbr/Smarcd3^tm1.1Bbr Tg(Myh6-cre)2182Mds/0	either: (involves: 129 * C57BL/6 * FVB/N * SJL) or (involves: 129 * C57BL/6 * FVB/N * ICR * SJL)	MGI:6368035
cn4	Hand1^tm1Eno/Hand1^tm2Eno Tg(Myh6-cre)2182Mds/0	either: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * C57BL/6)	MGI:3514054
cn5	Rb1^tm2Brn/Rb1^tm2Brn Rbl2^tm1Tyj/Rbl2^tm1Tyj Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds	involves: 129 * 129S2/SvPas * FVB/N	MGI:3710679
cn6	Cxadr^tm1Know/Cxadr^tm1Know Tg(Myh6-cre)2182Mds/0	involves: 129 * Black Swiss * FVB/N	MGI:3815088
cn7	Med13^tm1Eno/Med13^tm1Eno Tg(Myh6-cre)2182Mds/0	involves: 129 * C57BL/6 * FVB/N	MGI:5431523
cn8	Gata4^tm1Grg/Gata4^tm1.1Wtp Tg(Myh6-cre)2182Mds/0	involves: 129 * C57BL/6 * FVB/N	MGI:5427939
cn9	Jup^tm1.1Shou/Jup^tm1.1Shou Tg(Myh6-cre)2182Mds/0	involves: 129 * C57BL/6J	MGI:5296512
cn10	Eif4ebp1^tm1Nso/Eif4ebp1^tm1Nso Rheb^tm1.1Otsu/Rheb^tm1.1Otsu Tg(Myh6-cre)2182Mds/0	involves: 129 * C57BL/6J * FVB/N	MGI:5502748
cn11	Rheb^tm1.1Otsu/Rheb^tm1.1Otsu Tg(Myh6-cre)2182Mds/0	involves: 129 * C57BL/6J * FVB/N	MGI:5502747
cn12	Rb1^tm2Brn/Rb1^tm2Brn Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds	involves: 129 * FVB	MGI:3710677
cn13	Hprt1^tm2(CAG-TBX2,-EGFP)Akis/Hprt1^+ Tg(Myh6-cre)2182Mds/0	involves: 129 * FVB/N * NMRI	MGI:5314543
cn14	Srf^tm1Rjs/Srf^tm2.1Nor Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:3608600
cn15	Mdm4^tm2Glo/Mdm4^tm2.1Glo Tg(Myh6-cre)2182Mds/0 Trp53^tm1Tyj/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S/Sv * C57BL/6J * FVB/N	MGI:5907135
cn16	Gja1^tm10Kwi/Gja1^tm10Kwi Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5477915
cn17	Cxcr4^tm2Yzo/Cxcr4^tm2Yzo Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:7261455
cn18	Gjc1^tm1.1(Gjd2)Kwi/Gjc1^tm1.1(Gjd2)Kwi Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL	MGI:5317174
cn19	Stat3^tm1Vpo/Stat3^tm1Vpo Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * FVB/N	MGI:5906908
cn20	Stat3^tm1Vpo/Stat3^+ Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * FVB/N	MGI:5906909
cn21	Ncoa6^tm1Jkr/Ncoa6^tm1Jkr Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * FVB/N	MGI:6276351
cn22	Ncoa6^tm1Jkr/Ncoa6^+ Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * FVB/N	MGI:6276352
cn23	Med1^tm2Jkr/Med1^tm2Jkr Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * FVB/N	MGI:5911326
cn24	Zfpm2^tm1Sho/Zfpm2^tm2Sho Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:3851401
cn25	Gt(ROSA)26Sor^tm2(Mib1)Jlp/Gt(ROSA)26Sor^+ Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7544914
cn26	Gt(ROSA)26Sor^tm1(Mib1*V943F)Jlp/Gt(ROSA)26Sor^+ Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7544917
cn27	Npr1^tm1Kuhn/Npr1^tm1Kuhn Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:3687001
cn28	Gab1^tm1Nmoc/Gab1^tm1Nmoc Gab2^tm1Thir/Gab2^tm1Thir Tg(Myh6-cre)2182Mds/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:3721269
cn29	Shc1^tm8Paw/Shc1^tm9.1Paw Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3717096
cn30	Cxadr^tm1Mds/Cxadr^tm1.1Mds Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3711512
cn31	Cxadr^tm1Mds/Cxadr^tm1Mds Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3711507
cn32	Jarid2^tm1Yskl/Jarid2^tm1Yskl Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3689723
cn33	Acvr1^tm1Vk/Acvr1^tm1.1Vk Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3697609
cn34	Stat3^tm1Xyfu/Stat3^tm1.1Xyfu Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * FVB/N	MGI:4879018
cn35	Stat3^tm1Xyfu/Stat3^+ Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * FVB/N	MGI:4879021
cn36	Mdm4^tm2Glo/Mdm4^tm2.1Glo Tg(Myh6-cre)2182Mds/0 Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:5907132
cn37	Mdm2^tm1Glo/Mdm2^tm2.1Glo Tg(Myh6-cre)2182Mds/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129S7/SvEvBrd * FVB/N	MGI:3616710
cn38	Gja1^tm8Kwi/Gja1^+ Tg(Myh6-cre)2182Mds/0	involves: 129S2/SvPas * FVB/N	MGI:3807709
cn39	Mecp2^tm1Jae/Y Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * FVB/N	MGI:6098758
cn40	Fstl1^tm1.1Mvdh/Fstl1^tm1.1Mvdh Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJae * C57BL/6 * FVB/N	MGI:5297552
cn41	Ddt^tm1Lhy/Ddt^tm1Lhy Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJae * C57BL/6 * FVB/N	MGI:6705053
cn42	Vhl^tm1Jae/Vhl^tm1Jae Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJae * FVB/N	MGI:5304714
cn43	Mef2c^tm1Eno/Mef2c^tm1Jjs Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * 129S7/SvEvBrd * FVB/N	MGI:3613580
cn44	Mdm4^tm2Glo/Mdm4^tm2.1Glo Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:3616711
cn45	Bdh1^tm1c(EUCOMM)Wtsi/Bdh1^tm1c(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJaeSor * C57BL/6 * FVB/N	MGI:6303767
cn46	Grk5^tm2Rjl/Grk5^tm2Rjl Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJaeSor * C57BL/6J * FVB/N	MGI:5582621
cn47	Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJaeSor * FVB/N	MGI:5829559
cn48	Gata4^tm1Sho/Gata4^+ Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac	MGI:3851413
cn49	Gata4^tm1Sho/Gata4^tm1.1Wtp Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3851409
cn50	Esrrb^tm1.1Nat/Esrrb^tm1.1Nat Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * FVB/N	MGI:5905569
cn51	Ptpn11^tm6Bgn/Ptpn11^+ Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:3840255
cn52	Ednra^tm2Ywa/Ednra^tm2Ywa Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:2687389
cn53	Myh10^tm7Rsad/Myh10^tm7Rsad Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:4946095
cn54	Ptger4^tm1.1Matb/Ptger4^tm1.1Matb Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * FVB/N	MGI:5906377
cn55	Edn1^tm1Ywa/Edn1^tm1Ywa Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * FVB/N	MGI:3044594
cn56	Men1^tm1.2Ctre/Men1^tm1.2Ctre Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * FVB/N	MGI:7344039
cn57	Egln1^tm1Kael/Egln1^tm1Kael Egln3^tm1Vlcg/Egln3^tm1Vlcg Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * FVB/N	MGI:5304713
cn58	Egln1^tm1Kael/Egln1^tm1Kael Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * FVB/N	MGI:5304715
cn59	Gt(ROSA)26Sor^tm4(HIF2A*)Kael/Gt(ROSA)26Sor^+ Tg(Myh6-cre)2182Mds/0	involves: 129S6/SvEvTac * FVB/N	MGI:5304716
cn60	Tbx1^tm1Bld/Tbx1^tm3Bld Tg(Myh6-cre)2182Mds/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:3046803
cn61	Mdm2^tm1Glo/Mdm2^tm2.1Glo Tg(Myh6-cre)2182Mds/0	involves: 129S7/SvEvBrd * FVB/N	MGI:3616709
cn62	Rassf1^tm1.1Brd/Rassf1^tm1.1Brd Tg(Myh6-cre)2182Mds/0	involves: 129S7/SvEvBrd * FVB/N	MGI:4837486
cn63	Dicer1^tm1Smr/Dicer1^tm1Smr Tg(Myh6-cre)2182Mds/0	involves: 129S7/SvEvBrd * FVB/N	MGI:5906349
cn64	Fkbp1a^tm1.1Shou/Fkbp1a^tm1Zuk Tg(Myh6-cre)2182Mds/0	involves: 129S7/SvEvBrd * FVB/N	MGI:5490257
cn65	Hdac3^tm1.1Eno/Hdac3^tm1.1Eno Tg(Myh6-cre)2182Mds/?	involves: 129S/SvEv * C57BL/6	MGI:3831703
cn66	Hdac1^tm1.1Eno/Hdac1^tm1.1Eno Hdac2^tm1.1Eno/Hdac2^tm1.1Eno Tg(Myh6-cre)2182Mds/?	involves: 129S/SvEv * C57BL/6 * CD-1 * FVB/N	MGI:3718388
cn67	Hdac1^tm1.1Eno/Hdac1^tm1.1Eno Tg(Myh6-cre)2182Mds/?	involves: 129S/SvEv * C57BL/6 * CD-1 * FVB/N	MGI:3718385
cn68	Hdac2^tm1.1Eno/Hdac2^tm1.1Eno Tg(Myh6-cre)2182Mds/?	involves: 129S/SvEv * C57BL/6 * CD-1 * FVB/N	MGI:3718387
cn69	Prkd1^tm1Eno/Prkd1^tm1Eno Tg(Myh6-cre)2182Mds/?	involves: 129S/SvEv * C57BL/6 * FVB/N	MGI:3778390
cn70	Atg5^tm1Myok/Atg5^tm1Myok Tg(Myh6-cre)2182Mds/?	involves: 129S/SvEv * C57BL/6 * FVB/N	MGI:3713114
cn71	Atg5^tm1Myok/Atg5^tm1Myok Rheb^tm1.1Otsu/Rheb^tm1.1Otsu Tg(Myh6-cre)2182Mds/0	involves: 129S/SvEv * C57BL/6J * FVB/N	MGI:5502749
cn72	Yap1^tm1.1Eno/Yap1^tm1.1Eno Tg(Myh6-cre)2182Mds/0	involves: 129S/SvEv * FVB/N	MGI:5544295
cn73	Wwtr1^tm1.1Eno/Wwtr1^tm1.1Eno Tg(Myh6-cre)2182Mds/0	involves: 129S/SvEv * FVB/N	MGI:5544299
cn74	Wwtr1^tm1.1Eno/Wwtr1^tm1.1Eno Yap1^tm1.1Eno/Yap1^tm1.1Eno Tg(Myh6-cre)2182Mds/0	involves: 129S/SvEv * FVB/N	MGI:5544298
cn75	Wwtr1^tm1.1Eno/Wwtr1^tm1.1Eno Yap1^tm1.1Eno/Yap1^+ Tg(Myh6-cre)2182Mds/0	involves: 129S/SvEv * FVB/N	MGI:5544296
cn76	Wwtr1^tm1.1Eno/Wwtr1^+ Yap1^tm1.1Eno/Yap1^tm1.1Eno Tg(Myh6-cre)2182Mds/0	involves: 129S/SvEv * FVB/N	MGI:5544297
cn77	Rock2^tm2Liao/Rock2^tm2Liao Tg(Myh6-cre)2182Mds/?	involves: 129/Sv * C57BL/6	MGI:5491820
cn78	Myocd^tm1Msp/Myocd^tm1Msp Tg(Myh6-cre)2182Mds/0	involves: 129/Sv * FVB/N	MGI:5907041
cn79	Ppargc1a^tm1Dpk/Ppargc1a^tm1Dpk Ppargc1b^tm1Dpk/Ppargc1b^tm1Dpk Tg(Myh6-cre)2182Mds/0	involves: 129X1/SvJ * FVB/N	MGI:3802663
cn80	Lemd2^em2Eno/Lemd2^em2Eno Tg(Myh6-cre)2182Mds/0	involves: C3H * C57BL/6 * C57BL/6N * FVB/N	MGI:7444863
cn81	Abl1^tm1Goff/Abl1^tm1Goff Tg(Myh6-cre)2182Mds/0	involves: C57BL/6	MGI:4421539
cn82	Lpl^tm1Ijg/Lpl^tm1Ijg Tg(Myh6-cre)2182Mds/?	involves: C57BL/6	MGI:3045423
cn83	Rce1^tm2Kim/Rce1^tm2.1Kim Tg(Myh6-cre)2182Mds/0	involves: C57BL/6	MGI:3032514
cn84	Nsun3^tm1.1Tomik/Nsun3^tm1.1Tomik Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * C57BL/6J * FVB/N	MGI:7718681
cn85	Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * C57BL/6NCrl * FVB/N	MGI:5805256
cn86	Oma1^tm1Tlan/Oma1^tm1Tlan Yme1l1^tm1Tlan/Yme1l1^tm1Tlan Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * C57BL/6NCrl * FVB/N	MGI:5805258
cn87	Creld1^tm1c(EUCOMM)Wtsi/Creld1^tm1c(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * C57BL/6N * FVB/N * SJL	MGI:7546788
cn88	Nox4^tm1.1Jusa/Nox4^tm1.1Jusa Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * FVB	MGI:4830886
cn89	Fdps^tm1Jiy/Fdps^tm1Jiy Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * FVB/N	MGI:6857772
cn90	Rbm20^tm2.1Hgra/Rbm20^+ Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * FVB/N	MGI:5566535
cn91	Klf5^tm2.1Rng/Klf5^tm2.1Rng Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * FVB/N	MGI:4421818
cn92	Atp6ap2^tm1.1Aich/Y Tg(Myh6-cre)2182Mds/?	involves: C57BL/6 * FVB/N	MGI:4836055
cn93	Nr3c1^tm1.1Jaci/Nr3c1^tm1.1Jaci Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * FVB/N	MGI:5526029
cn94	Hey2^tm2.1Mtc/Hey2^tm2.1Mtc Tg(Myh6-cre)2182Mds/0	involves: C57BL/6 * FVB/N * SJL	MGI:5433520
cn95	Map3k5^tm1Hijo/Map3k5^tm1Hijo Raf1^tm2Bacc/Raf1^tm2Bacc Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J	MGI:3510548
cn96	Mapk14^tm1.2Otsu/Mapk14^tm1.2Otsu Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J	MGI:3525858
cn97	Raf1^tm2Bacc/Raf1^tm2Bacc Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J	MGI:3510547
cn98	Cap2^tm1c(EUCOMM)Wtsi/Cap2^tm1c(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J * C57BL/6N	MGI:5806895
cn99	Trim29^tm1c(EUCOMM)Wtsi/Trim29^tm1c(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J * C57BL/6N * C57BL/6NTac	MGI:7662823
cn100	Nae1^tm1c(EUCOMM)Wtsi/Nae1^tm1c(EUCOMM)Wtsi Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J * C57BL/6N * FVB/N * SJL	MGI:6159290
cn101	Snrk^tm2Rra/Snrk^tm2Rra Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J * FVB/N	MGI:5792710
cn102	Snrk^tm2Rra/Snrk^+ Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J * FVB/N	MGI:5792711
cn103	Capns1^tm1.1Otsu/Capns1^tm1.1Otsu Tg(Myh6-cre)2182Mds/0	involves: C57BL/6J * FVB/N	MGI:5293311
cn104	Mtfp1^tm1.2Wait/Mtfp1^tm1.2Wait Tg(Myh6-cre)2182Mds/0	involves: C57BL/6N * FVB/N	MGI:7596339
cn105	Acad9^tm1c(KOMP)Wtsi/Acad9^tm1c(KOMP)Wtsi Tg(Myh6-cre)2182Mds/0	involves: C57BL/6N * FVB/N	MGI:7378415
cn106	Lpl^tm1Ijg/Lpl^tm1Ijg Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:3655840
cn107	Gata4^tm1.1Wtp/Gata4^tm1.1Wtp Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:3639277
cn108	Tg(ACTB-EGFP,-Kcnj8*)1Wco/0 Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:6275067
cn109	Ehmt1^tm2Yshk/Ehmt1^tm2Yshk Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:5543777
cn110	Tg(CAG-cat,-TBX3)1Vmc/0 Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:5314604
cn111	Fkbp1a^tm1.1Shou/Fkbp1a^tm1.1Shou Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:5319195
cn112	Hand1^tm5Abfi/Hand1^+ Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:6766588
cn113	Map3k7^tm1Mds/Map3k7^tm1Mds Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:3696414
cn114	Tg(CAG-Map3k7*K63W)1232Mds/0 Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:4461321
cn115	Cxadr^tm1Mgot/Cxadr^tm1Mgot Tg(Myh6-cre)2182Mds/0	involves: FVB/N	MGI:3812382
cn116	Gja1^tm1Gfi/Gja1^tm1Gfi Tg(Myh6-cre)2182Mds/0	Not Specified	MGI:3051890
cn117	Ttn^tm1Her/Ttn^tm1Her Tg(Myh6-cre)2182Mds/0	Not Specified	MGI:2651646
tg118	Tg(Myh6-cre)2182Mds/0	Not Specified	MGI:5526034

Genotype
MGI:3706583

cn1

• Allelic Composition: Ctnnb1^{tm2(Nfkbia)Rsu}/Ctnnb1⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: B6.Cg-Ctnnb1^{tm2(Nfkbia)Rsu} Tg(Myh6-cre)2182Mds

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cardiovascular system

decreased response of heart to induced stress ( J:111645 )

• mutants display an attenuated hypertrophic response compared with controls upon infusion of angiotensin II or isoproterenol as well as reduced expression of hypertrophy markers

homeostasis/metabolism

decreased response of heart to induced stress ( J:111645 )

• mutants display an attenuated hypertrophic response compared with controls upon infusion of angiotensin II or isoproterenol as well as reduced expression of hypertrophy markers

Genotype
MGI:5823159

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm3(CAG-EYFP)Hze}/Gt(ROSA)26Sor⁺; Hira^{tm1c(EUCOMM)Wtsi}/Hira^{tm1d(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-EYFP)Hze} Hira^{tm1c(EUCOMM)Wtsi}/Hira^{tm1d(EUCOMM)Wtsi} Tg(Myh6-cre)2182Mds
• Cell Lines: EPD0181_1_A05

cardiovascular system

abnormal heart morphology ( J:231593 )

• hearts show re-expression of fetal cardiac genes

• however, heart development proceeds normally

abnormal myocardial fiber morphology ( J:231593 )

• hypertrophic cardiomyocytes are seen in the right ventricle free wall as early as 15 days after birth

• however, aberrant proliferation of or apoptosis of cardiomyocytes is not seen and there is no evidence of increased DNA damage

myocardial fiber degeneration ( J:231593 )

• lesions contain degenerating cardiomyocytes

cardiac fibrosis ( J:231593 )

• hearts at 6 weeks and 6 months of age exhibit white surface scars localized to the subepicardial region of the ventricular free walls; lesions contain degenerating cardiomyocytes and a large degree of collagen deposition indicating focal replacement fibrosis localized to the subepicardial myocardium

abnormal cardiovascular system physiology ( J:231593 )

• mice show increased arterial elastance at 6 months of age, which is a measure of arterial load

• the slope of the end-diastolic pressure-volume relationship, which describes diastolic function, is elevated

• however, no effect is seen on the slope of end-systolic pressure-volume relationship, which describes the maximal developed ventricular pressure at any given ventricular volume

abnormal blood circulation ( J:231593 )

• mice show decreased stroke work at 6 months

decreased cardiac output ( J:231593 )

• at 6 months of age

decreased cardiac stroke volume ( J:231593 )

• at 6 months of age

abnormal cardiac muscle contractility ( J:231593 )

• mice exhibit increased dp/dtmax-end-diastolic volume, the relationship between peak rate of pressure rise and EDV, which describes ventricular contractile performance

abnormal myocardial fiber physiology ( J:231593 )

• mice show an increase in diastolic myocardial stiffness

congestive heart failure ( J:231593 )

cellular

oxidative stress ( J:231593 )

• levels of manganese superoxide dismutase are reduced in scar-containing free-wall right ventricle, but not in non-scarred regions, suggesting impaired response to oxidative stress

• however, only very minor increases in reactive oxygen species are seen, indicating that cardiomyocyte degeneration most likely is not caused by increased oxidative stress

muscle

abnormal myocardial fiber morphology ( J:231593 )

• hypertrophic cardiomyocytes are seen in the right ventricle free wall as early as 15 days after birth

• however, aberrant proliferation of or apoptosis of cardiomyocytes is not seen and there is no evidence of increased DNA damage

myocardial fiber degeneration ( J:231593 )

• lesions contain degenerating cardiomyocytes

abnormal cardiac muscle contractility ( J:231593 )

• mice exhibit increased dp/dtmax-end-diastolic volume, the relationship between peak rate of pressure rise and EDV, which describes ventricular contractile performance

abnormal sarcolemma morphology ( J:231593 )

• cardiomyocyte sarcolemmal integrity is compromised in focal subepicardial areas between 15 and 25 days after birth

Genotype
MGI:6368035

cn3

• Allelic Composition: Smarcd3^tm1.1Bbr/Smarcd3^tm1.1Bbr; Tg(Myh6-cre)2182Mds/0
• Genetic Background: either: (involves: 129 * C57BL/6 * FVB/N * SJL) or (involves: 129 * C57BL/6 * FVB/N * ICR * SJL)

mortality/aging

premature death ( J:257963 )

• all mice die before 4 months of age

postnatal lethality, incomplete penetrance ( J:257963 )

• some pups show delayed growth after P7 and die before weaning

growth/size/body

enlarged heart ( J:257963 )

• hearts are larger at P10, P21, and 8 weeks of age

postnatal growth retardation ( J:257963 )

• some pups show delayed growth after P7

cardiovascular system

abnormal intercalated disk morphology ( J:257963 )

• localization of desmin in intercalated discs is reduced and pattern of desmin localization is perturbed

enlarged heart ( J:257963 )

• hearts are larger at P10, P21, and 8 weeks of age

thin ventricular wall ( J:257963 )

• thinner anterior and posterior ventricle walls

cardiac interstitial fibrosis ( J:257963 )

• broad myocardium interstitial fibrosis

dilated heart ( J:257963 )

• chamber dilation

dilated heart left ventricle ( J:257963 )

decreased cardiac output ( J:257963 )

• in 8 week old hearts

decreased cardiac muscle contractility ( J:257963 )

• 8 week old hearts show reduced fractional shortening and decreased chamber contraction ratio

abnormal heart echocardiography feature ( J:257963 )

• echocardiography of 8 week old hearts indicates dilated left ventricles, thinner anterior and posterior ventricle walls, decreased chamber contraction ratio, increased aortic time-velocity integral (the distance traveled by a volume of blood during a time interval), reduced fractional shortening and cardiac output

decreased heart rate ( J:257963 )

shortened PR interval ( J:257963 )

• mice exhibit shortened conduction time through the atrioventricular node (PR interval)

decreased P wave amplitude ( J:257963 )

• P wave height, which indicates atrial depolarization, is reduced

increased QRS amplitude ( J:257963 )

prolonged QRS complex duration ( J:257963 )

prolonged QT interval ( J:257963 )

congestive heart failure ( J:257963 )

• some mice survive after weaning without obvious defects, but at 4-6 weeks exhibit symptoms of heart failure, including weight loss, reduced activity level, hunched back and labored breath

muscle

abnormal intercalated disk morphology ( J:257963 )

• localization of desmin in intercalated discs is reduced and pattern of desmin localization is perturbed

decreased cardiac muscle contractility ( J:257963 )

• 8 week old hearts show reduced fractional shortening and decreased chamber contraction ratio

increased cardiomyocyte apoptosis ( J:257963 )

• high level of apoptosis in the myocardium

abnormal sarcomere morphology ( J:257963 )

• sarcomere length in cardiomyocytes is shorter

cellular

cardiac interstitial fibrosis ( J:257963 )

• broad myocardium interstitial fibrosis

increased cardiomyocyte apoptosis ( J:257963 )

• high level of apoptosis in the myocardium

Genotype
MGI:3514054

cn4

• Allelic Composition: Hand1^tm1Eno/Hand1^tm2Eno; Tg(Myh6-cre)2182Mds/0
• Genetic Background: either: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * C57BL/6)

mortality/aging

postnatal lethality, incomplete penetrance ( J:94514 )

• most mutants die within 3 days of birth with only 4% surviving to P10 and less than 2% reaching adulthood

cardiovascular system

abnormal atrioventricular cushion morphology ( J:94514 )

• immature endocardial cushions are seen in mutant hearts at E13.5

double outlet right ventricle ( J:94514 )

overriding aortic valve ( J:94514 )

abnormal atrioventricular valve morphology ( J:94514 )

• hyperplastic atrioventicular valves are seen in all mutants and these valves are thickened in neonates

perimembraneous ventricular septal defect ( J:94514 )

• 90% of mutants have membranous ventricular septal defects and these defects can be detected as early as E10.5

abnormal interventricular septum muscular part morphology ( J:94514 )

• the muscular ventricular septum is thickened and disorganized

decreased heart left ventricle size ( J:94514 )

• at E11.5 and E13.5 the left ventricle is reduced in size, however the size is normal at birth

homeostasis/metabolism

cyanosis ( J:94514 )

• most mutants become cyanotic within 3 days of birth

Genotype
MGI:3710679

cn5

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl2^tm1Tyj/Rbl2^tm1Tyj; Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
• Genetic Background: involves: 129 * 129S2/SvPas * FVB/N

mortality/aging

premature death ( J:97589 )

• 36% die suddenly by 12 weeks of age and only 48% survive to 6 months of age

cardiovascular system

increased myocardial fiber size ( J:97589 )

• cardiomyocytes have an increase in diameter and contain large, hyperchromatic nuclei

enlarged heart ( J:97589 )

• mutants exhibit a 3-fold increase in the heart weight-to-body weight ratio at 8 weeks of age but not in the neonatal time period

dilated heart left ventricle ( J:97589 )

• mutants surviving to 12 weeks of age show evidence of LV dilation

decreased heart left ventricle muscle contractility ( J:97589 )

• end-diastolic diameter and end-systolic diameter are increased and left ventricular fractional shortening and circumferential shortening velocity are decreased in mutants surviving to 12 seeks of age, indicating left ventricular systolic dysfunction

decreased heart rate ( J:97589 )

• seen in mutants surviving to 12 weeks of age

abnormal myocardial fiber physiology ( J:97589 )

• hearts exhibit persistent myocyte cycling

respiratory system

respiratory distress ( J:97589 )

• 36% develop signs of respiratory distress

homeostasis/metabolism

edema ( J:97589 )

• 36% develop signs of generalized edema

muscle

increased myocardial fiber size ( J:97589 )

• cardiomyocytes have an increase in diameter and contain large, hyperchromatic nuclei

decreased heart left ventricle muscle contractility ( J:97589 )

• end-diastolic diameter and end-systolic diameter are increased and left ventricular fractional shortening and circumferential shortening velocity are decreased in mutants surviving to 12 seeks of age, indicating left ventricular systolic dysfunction

growth/size/body

enlarged heart ( J:97589 )

• mutants exhibit a 3-fold increase in the heart weight-to-body weight ratio at 8 weeks of age but not in the neonatal time period

Genotype
MGI:3815088

cn6

• Allelic Composition: Cxadr^tm1Know/Cxadr^tm1Know; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * Black Swiss * FVB/N

cardiovascular system

abnormal intercalated disk morphology ( J:140870 )

• 8-week old mice have a clear decrease in ZO-1 localized to the intercalated disc

• intercalated discs are punctuated by areas where there is an increase in the space between cardiac myocytes, usually near the adherens junctions

• disorganization of the electron-dense structures associated with the intercalated disc is observed

• disorganization of the myofilaments that attach to the intercalated disc also occurs

cardiac fibrosis ( J:140870 )

• cardiac fibrosis occurs in mice 25 weeks of age

decreased cardiac muscle contractility ( J:140870 )

• there is a progressive decrease in fractional shortening at 21 and 25 weeks of age

• fractional shortening degrades from a normal level at 17 weeks of age to half that of wild-type by 25 weeks of age

shortened RR interval ( J:140870 )

• the R-to-R intervals are shorter in these mice with 127.3 ms in wild-type mice vs. 97.4 ms in mutant mice

atrioventricular block ( J:140870 )

• AV-node block occurs in these mice with half the mice having a complete AV block and the other half having first-degree AV block over 90% of the time

prolonged PR interval ( J:140870 )

• in mice without complete AV blockage, there is an extended PR interval

• mean PR interval is 36.5 ms in wild-type compared with 53.9 ms in mutant mice

absent P wave ( J:140870 )

• an averaged P-wave is not detectable because of the dissociation between the atrial and the ventricular depolarizations

muscle

abnormal intercalated disk morphology ( J:140870 )

• 8-week old mice have a clear decrease in ZO-1 localized to the intercalated disc

• intercalated discs are punctuated by areas where there is an increase in the space between cardiac myocytes, usually near the adherens junctions

• disorganization of the electron-dense structures associated with the intercalated disc is observed

• disorganization of the myofilaments that attach to the intercalated disc also occurs

decreased cardiac muscle contractility ( J:140870 )

• there is a progressive decrease in fractional shortening at 21 and 25 weeks of age

• fractional shortening degrades from a normal level at 17 weeks of age to half that of wild-type by 25 weeks of age

Genotype
MGI:5431523

cn7

• Allelic Composition: Med13^tm1Eno/Med13^tm1Eno; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:186193 )

• in mice fed a high fat diet

increased circulating insulin level ( J:186193 )

• in mice fed a high fat diet

increased circulating leptin level ( J:186193 )

• in mice fed a high fat diet

increased circulating cholesterol level ( J:186193 )

• in mice fed a high fat diet

increased circulating triglyceride level ( J:186193 )

• in mice fed a high fat diet

impaired glucose tolerance ( J:186193 )

• in mice fed a high fat diet

increased liver triglyceride level ( J:186193 )

• in mice fed a high fat diet

adipose tissue

increased brown adipose tissue amount ( J:186193 )

• increased subscapular fat pad in mice fed a high fat diet

increased abdominal adipose tissue amount ( J:186193 )

• mice fed a high fat diet exhibit increased visceral white adipose tissue compared with wild-type mice

increased total body fat amount ( J:186193 )

• dramatic in mice fed a high fat diet

increased white fat cell size ( J:186193 )

• in mice fed a high fat diet

growth/size/body

increased lean body mass ( J:186193 )

• small in mice fed a high fat diet

increased body weight ( J:186193 )

• in mice fed a high fat diet

increased susceptibility to diet-induced obesity ( J:186193 )

• in mice fed a high fat diet

increased liver weight ( J:186193 )

• in mice fed a high fat diet

cardiovascular system

cardiovascular system phenotype ( J:186193 )

N • mice exhibit normal cardiac morphology and physiology

liver/biliary system

increased liver weight ( J:186193 )

• in mice fed a high fat diet

increased liver triglyceride level ( J:186193 )

• in mice fed a high fat diet

Genotype
MGI:5427939

cn8

• Allelic Composition: Gata4^tm1Grg/Gata4^tm1.1Wtp; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

Hearts of Gata4^tm1.1Wtp/Gata4^tm1Grg Tg(Myh6-cre)2182Mds/0 mice appear normal

normal phenotype

no abnormal phenotype detected ( J:185124 )

• viable with no signs of embryonic growth retardation or myocardial thinning

Genotype
MGI:5296512

cn9

• Allelic Composition: Jup^tm1.1Shou/Jup^tm1.1Shou; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * C57BL/6J

mortality/aging

premature death ( J:177567 )

• mutants suddenly die starting at 1 month of age, with an average life-span of 4.6 months

cardiovascular system

liver vascular congestion ( J:177567 )

• mutants exhibit severe liver congestion

abnormal myocardial fiber morphology ( J:177567 )

• cardiomyocytes are hypertrophic, showing an increase in cross-sectional area

• hearts show loss of desmosomes, however adherens junctions are normal

calcified myocardium ( J:177567 )

• myocardial calcification is seen in 2-month old ventricles

cardiac muscle necrosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

increased heart right atrium size ( J:177567 )

enlarged heart ( J:177567 )

• heart is enlarged at 2 months of age

abnormal heart ventricle morphology ( J:177567 )

• hearts exhibit regional dysplasia of ventricular walls and ventricular aneurysms

ventricular aneurysm ( J:177567 )

cardiac fibrosis ( J:177567 )

• cardiac fibrosis is seen in atria and ventricles; fibrosis ranges from moderate to severe

dilated heart ( J:177567 )

dilated heart right ventricle ( J:177567 )

abnormal cardiovascular system physiology ( J:177567 )

• ECG shows compromised systolic function of the left ventricle

• fragmented diastolic potentials are seen in right ventricle

decreased cardiac muscle contractility ( J:177567 )

• hearts show reduced fractional shortening and ejection fraction

ventricular tachycardia ( J:177567 )

• at 1 and 2 months of age, mutants exhibit spontaneous non-sustained ventricular tachycardia

• sustained monomorphic ventricular tachycardias are induced in mutants by bust or programmed ventricular stimulation in 6 of 7 mutants but not in controls

• mutants exhibit intracardiac bipolar electrograms during ventricular tachycardia

abnormal impulse conducting system conduction ( J:177567 )

• in Langendorff-perfused hearts, conduction velocity max and min are reduced

abnormal heart electrocardiography waveform feature ( J:177567 )

• at 1 month of age, mutants exhibit complex electrophysiological abnormalities, with low amplitude of the QRS complex, prolonged PR interval and spontaneous non-sustained ventricular tachycardia

• by 2 months of age, the amplitude of the P-wave is higher, amplitude of QRS complex is lower, the PR interval is prolonged, and frequent spontaneous ventricular ectopic beats are seen

prolonged PR interval ( J:177567 )

• at 1 and 2 months of age, mutants exhibit prolonged PR interval

abnormal P wave ( J:177567 )

• by 2 months of age, the amplitude of the P-wave is higher

decreased QRS amplitude ( J:177567 )

• ECG shows decreased QRS complex amplitude at P18, 1 month and 2 months of age

cardiomyopathy ( J:177567 )

• mutants show rapid and progressive development of cardiomyopathy; hearts appear normal at P12 but by P18, show signs of fibrosis and heart enlargement by 1 month

liver/biliary system

liver vascular congestion ( J:177567 )

• mutants exhibit severe liver congestion

muscle

abnormal myocardial fiber morphology ( J:177567 )

• cardiomyocytes are hypertrophic, showing an increase in cross-sectional area

• hearts show loss of desmosomes, however adherens junctions are normal

calcified myocardium ( J:177567 )

• myocardial calcification is seen in 2-month old ventricles

cardiac muscle necrosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

decreased cardiac muscle contractility ( J:177567 )

• hearts show reduced fractional shortening and ejection fraction

cardiomyopathy ( J:177567 )

• mutants show rapid and progressive development of cardiomyopathy; hearts appear normal at P12 but by P18, show signs of fibrosis and heart enlargement by 1 month

increased cardiomyocyte apoptosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

cellular

increased cardiomyocyte apoptosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

growth/size/body

enlarged heart ( J:177567 )

• heart is enlarged at 2 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arrhythmogenic right ventricular dysplasia 12		DOID:0110083	OMIM:611528	J:177567

Genotype
MGI:5502748

cn10

• Allelic Composition: Eif4ebp1^tm1Nso/Eif4ebp1^tm1Nso; Rheb^tm1.1Otsu/Rheb^tm1.1Otsu; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:197831 )

• improved survival compared to in Rheb^tm1.1Otsu/Rheb^tm1.1Otsu Tg(Myh6-cre)2182Mds mice

cardiovascular system

cardiovascular system phenotype ( J:197831 )

N • mice exhibit improved cardiac function, hypertrophic growth and sarcomere maturation compared with Rheb^tm1.1Otsu/Rheb^tm1.1Otsu Tg(Myh6-cre)2182Mds mice

Genotype
MGI:5502747

cn11

• Allelic Composition: Rheb^tm1.1Otsu/Rheb^tm1.1Otsu; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/N

Sarcomere maturation is attenuated in Rheb^tm1.1Otsu/Rheb^tm1.1Otsu Tg(Myh6-cre)2182Mds/0 hearts

mortality/aging

postnatal lethality, complete penetrance ( J:197831 )

• mice die between P8 and P10

cardiovascular system

decreased myocardial fiber size ( J:197831 )

• at P8

thin interventricular septum ( J:197831 )

decreased heart weight ( J:197831 )

• at P8

abnormal heart left ventricle morphology ( J:197831 )

• reduced diastolic left ventricle posterior wall thickness

• larger end-diastolic and systolic dimensions

decreased cardiac muscle contractility ( J:197831 )

• reduced fractional shortening at P8

• however, cardiac function is normal until P5

cardiomyopathy ( J:197831 )

• without the involvement of autophagy

muscle

decreased myocardial fiber size ( J:197831 )

• at P8

decreased cardiac muscle contractility ( J:197831 )

• reduced fractional shortening at P8

• however, cardiac function is normal until P5

cardiomyopathy ( J:197831 )

• without the involvement of autophagy

abnormal sarcomere morphology ( J:197831 )

• sarcomere maturation is attenuated

Genotype
MGI:3710677

cn12

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(Myh6-cre)2182Mds/Tg(Myh6-cre)2182Mds
• Genetic Background: involves: 129 * FVB

normal phenotype

no abnormal phenotype detected ( J:97589 )

• mutants are born with the expected Mendelian distribution and adult show no change in heart size, myocyte cell distribution, myocyte apoptosis, or mechanical function

Genotype
MGI:5314543

cn13

• Allelic Composition: Hprt1^{tm2(CAG-TBX2,-EGFP)Akis}/Hprt1⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * FVB/N * NMRI

cardiovascular system

abnormal heart development ( J:181526 )

♀ • mice exhibit ectopic sub-endocardial mesenchyme in the atria and to a lesser extent in the ventricles unlike in control mice

♀ • mice exhibit abnormal cardiac jelly and cushion formation in chamber myocardium compared with control mice

Genotype
MGI:3608600

cn14

• Allelic Composition: Srf^tm1Rjs/Srf^tm2.1Nor; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:101311 )

• no viable embryos are found beyond E12.5

cardiovascular system

abnormal myocardium layer morphology ( J:101311 )

• sarcomere organization is disrupted in hearts

abnormal fetal atrioventricular canal morphology ( J:101311 )

• exhibit less constriction in the atrial ventricular canal at E10.5

abnormal heart ventricle morphology ( J:101311 )

• ventricular wall is hypoplastic with fewer trabeculae, ventricular wall compact layer is thinner, and cellular wall expansion is blocked

abnormal interventricular septum morphology ( J:101311 )

• intraventricular septation is less developed

abnormal interventricular groove morphology ( J:101311 )

• exhibit poorly developed intraventricular groove at E10.5

abnormal pericardium morphology ( J:101311 )

• dilated pericardial walls at E10.25

distended pericardium ( J:101311 )

• seen at E10.25

pericardial effusion ( J:101311 )

• show severe pericardial effusion at E11.5

irregular heartbeat ( J:101311 )

• lose rhythmic beating between E10.5 and E11.5

embryo

embryonic growth arrest ( J:101311 )

• some embryos arrest at the heart-looping stage (around E10.5-11.5)

muscle

abnormal myocardium layer morphology ( J:101311 )

• sarcomere organization is disrupted in hearts

increased cardiomyocyte apoptosis ( J:101311 )

homeostasis/metabolism

pericardial effusion ( J:101311 )

• show severe pericardial effusion at E11.5

cellular

increased cardiomyocyte apoptosis ( J:101311 )

Genotype
MGI:5907135

cn15

• Allelic Composition: Mdm4^tm2Glo/Mdm4^tm2.1Glo; Tg(Myh6-cre)2182Mds/0; Trp53^tm1Tyj/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv * C57BL/6J * FVB/N

mortality/aging

decreased tumor-free survival time ( J:137114 )

• mice die due to tumors not heart failure

extended life span ( J:137114 )

• mice show an extended mean survival of 403 days compared to compound heterozygous Mdm4^tm2Glo/Mdm4^tm2.1Glo conditional mutants

cardiovascular system

cardiovascular system phenotype ( J:137114 )

N • mice do not exhibit signs of heart failure such as edema and poor breathing and exhibit rescue of the dilated cardiomyopathy

neoplasm

increased tumor incidence ( J:137114 )

Genotype
MGI:5477915

cn16

• Allelic Composition: Gja1^tm10Kwi/Gja1^tm10Kwi; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:194957 )

• all mice die on the first day after birth

cardiovascular system

cardiovascular system phenotype ( J:194957 )

N • mice exhibit normal heart beating frequency, PQ duration and QRS amplitude

abnormal myocardial trabeculae morphology ( J:194957 )

• minor thickening and irregularities in the right ventricle

abnormal cardiac outflow tract development ( J:194957 )

• abnormal pouch formation at the subpulmonary outflow tract

• however, the outflow tract is open in neonates

prolonged QRS complex duration ( J:194957 )

• 3-fold at E16.5

muscle

abnormal myocardial trabeculae morphology ( J:194957 )

• minor thickening and irregularities in the right ventricle

Genotype
MGI:7261455

cn17

• Allelic Composition: Cxcr4^tm2Yzo/Cxcr4^tm2Yzo; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

premature death ( J:289614 )

• most mice die between 12-14 months of age

cardiovascular system

perivascular fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

abnormal heart morphology ( J:289614 )

• hearts from 5-month-old mice have a higher number of mitochondria and these mitochondria are smaller than in controls

• however, stroke volume and cardiac output are normal and heart rate is not significantly affected

abnormal myocardial fiber morphology ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

increased heart weight ( J:289614 )

• by 6 months of age, mice have a 15% increase in heart weight to body weight ratio and a 50% increase by 12 months of age

cardiac hypertrophy ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

• 4-month-old mice show elevated levels of atrial natriuretic factor (ANF), a maker of cardiac hypertrophy

cardiac interstitial fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

decreased heart ventricle muscle contractility ( J:289614 )

• 12-month-old mice exhibit a 3-fold decline in the maximum rate of change in left ventricular pressure (dp/dt max) and a more than 2.5-fold decline in ejection fraction

• 4-month-old mice exhibit a 2.5-fold decrease in contractility and a significant decrease in ejection fraction

decreased heart left ventricle muscle contractility ( J:289614 )

decreased left ventricle systolic pressure ( J:289614 )

• mice show an increase in left ventricular end-diastolic volume and an increase in end-systolic volume, indicating a decline in systolic pressures over time

cardiomyopathy ( J:289614 )

• mice develop progressive cardiomyopathy, showing mild cardiomyopathy as early as 4 months of age

congestive heart failure ( J:289614 )

• progressive cardiac dysfunction leads to clinical hear failure by 12 months of age

growth/size/body

increased heart weight ( J:289614 )

• by 6 months of age, mice have a 15% increase in heart weight to body weight ratio and a 50% increase by 12 months of age

cardiac hypertrophy ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

• 4-month-old mice show elevated levels of atrial natriuretic factor (ANF), a maker of cardiac hypertrophy

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:289614 )

• mice are more sensitive to catecholamine exposure via an acute isoproterenol challenge, showing a greater increase in ejection fraction and dp/dt max; mice show a robust response to isoproterenol and overcome their baseline deficits to eventually reach control levels, however the effect is only transient and cardiac function goes back to baseline within minutes

muscle

abnormal myocardial fiber morphology ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

decreased heart ventricle muscle contractility ( J:289614 )

• 12-month-old mice exhibit a 3-fold decline in the maximum rate of change in left ventricular pressure (dp/dt max) and a more than 2.5-fold decline in ejection fraction

• 4-month-old mice exhibit a 2.5-fold decrease in contractility and a significant decrease in ejection fraction

decreased heart left ventricle muscle contractility ( J:289614 )

cardiomyopathy ( J:289614 )

• mice develop progressive cardiomyopathy, showing mild cardiomyopathy as early as 4 months of age

cellular

cardiac interstitial fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:289614
congestive heart failure		DOID:6000		J:289614

Genotype
MGI:5317174

cn18

• Allelic Composition: Gjc1^{tm1.1(Gjd2)Kwi}/Gjc1^{tm1.1(Gjd2)Kwi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:182927 )

• at E11.5

cardiovascular system

abnormal atrioventricular cushion morphology ( J:182927 )

• fewer endocardial cells in the endocardial cushion tissue compared to in wild-type mice

enlarged heart ( J:182927 )

pericardial effusion ( J:182927 )

• by E10.5 and E11.5

dilated heart ( J:182927 )

• mild by E10.5 and E11.5

decreased cardiac muscle contractility ( J:182927 )

• hearts contract weakly until E11.5

decreased heart rate ( J:182927 )

• at E10.5, the beating frequency of atria and ventricles is reduced compared to in wild-type mice

abnormal impulse conducting system conduction ( J:182927 )

• at E10.5, mice exhibit impaired transmission atrial contraction impulses into the ventricles compared with wild-type mice

atrioventricular block ( J:182927 )

• at E10.5, most mice exhibit 2:1 or 3:1 AV blocks

congestive heart failure ( J:182927 )

• suggested by pericardial effusion and heart dilation at E10.5 and E11.5

embryo

embryonic growth retardation ( J:182927 )

• at E10.5 and E11.5

decreased embryo size ( J:182927 )

• at E10.5 and E11.5

growth/size/body

enlarged heart ( J:182927 )

embryonic growth retardation ( J:182927 )

• at E10.5 and E11.5

decreased embryo size ( J:182927 )

• at E10.5 and E11.5

homeostasis/metabolism

pericardial effusion ( J:182927 )

• by E10.5 and E11.5

muscle

decreased cardiac muscle contractility ( J:182927 )

• hearts contract weakly until E11.5

Genotype
MGI:5906908

cn19

• Allelic Composition: Stat3^tm1Vpo/Stat3^tm1Vpo; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

pregnancy-related premature death ( J:141591 )

• about 2/3 of females die after the second pregnancy

• no females survive more than 5 pregnancies

• death always occurs within the first 3 weeks after delivery

cardiovascular system

abnormal angiogenesis ( J:141591 )

• myocardial angiogenesis is impaired in postpartum females, with mice showing reduced left ventricle capillary density postpartum compared to controls

abnormal myocardial fiber morphology ( J:141591 )

• increase in cardiomyocyte length in postpartum females

cardiac fibrosis ( J:141591 )

• extensive cardiac fibrosis in postpartum females

dilated heart ( J:141591 )

• 4-chamber dilatation in postpartum females

dilated heart left ventricle ( J:141591 )

decreased cardiac muscle contractility ( J:141591 )

• depressed fractional shorting in postpartum females

abnormal heart echocardiography feature ( J:141591 )

• echocardiography indicates left ventricular dilatation and depressed fractional shorting in postpartum females

cardiomyopathy ( J:141591 )

• all females develop postpartum cardiomyopathy

• treatment with tetrakis (4-benzoic acid) porphyrin (MnTBAP), a pharmacological suppressor of ROS, partially suppresses postpartum cardiomyopathy

• treatment with bromocriptine, a dopamine-D2-receptor agonist and inhibitor of prolactin secretion, prevents postpartum cardiomyopathy and mortality in females

congestive heart failure ( J:141591 )

• after 2 pregnancies, the majority of females show signs of overt heart failure such as generalized edema and labored breathing

cellular

increased cardiomyocyte apoptosis ( J:141591 )

• cardiac apoptosis is increased in postpartum females

oxidative stress ( J:141591 )

• hearts of postpartum females exhibit increased oxidative stress

homeostasis/metabolism

abnormal atrial thrombosis ( J:141591 )

• thrombi are often seen in the atria of postpartum females

generalized edema ( J:141591 )

• females exhibit generalized edema after 2 pregnancies

muscle

abnormal myocardial fiber morphology ( J:141591 )

• increase in cardiomyocyte length in postpartum females

decreased cardiac muscle contractility ( J:141591 )

• depressed fractional shorting in postpartum females

cardiomyopathy ( J:141591 )

• all females develop postpartum cardiomyopathy

• treatment with tetrakis (4-benzoic acid) porphyrin (MnTBAP), a pharmacological suppressor of ROS, partially suppresses postpartum cardiomyopathy

• treatment with bromocriptine, a dopamine-D2-receptor agonist and inhibitor of prolactin secretion, prevents postpartum cardiomyopathy and mortality in females

increased cardiomyocyte apoptosis ( J:141591 )

• cardiac apoptosis is increased in postpartum females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
peripartum cardiomyopathy		DOID:9997		J:141591

Genotype
MGI:5906909

cn20

• Allelic Composition: Stat3^tm1Vpo/Stat3⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

pregnancy-related premature death ( J:141591 )

• postpartum cardiomyopathy-related death is seen after 3-4 deliveries

cardiovascular system

cardiomyopathy ( J:141591 )

• females develop postpartum cardiomyopathy

congestive heart failure ( J:141591 )

• after 4 pregnancies, the majority of females show signs of overt heart failure such as generalized edema and labored breathing

homeostasis/metabolism

generalized edema ( J:141591 )

• females exhibit generalized edema after 4 pregnancies

muscle

cardiomyopathy ( J:141591 )

• females develop postpartum cardiomyopathy

Genotype
MGI:6276351

cn21

• Allelic Composition: Ncoa6^tm1Jkr/Ncoa6^tm1Jkr; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:269856 )

• mice start to die after 2 months of age, with an approximate 40% survival at 8 months of age

cardiovascular system

abnormal heart morphology ( J:269856 )

• cardiac lipid accumulation

• hearts show disarray of mitochondria, a decrease in the number of mitochondria, and impaired activity of mitochondrial complex II

increased heart weight ( J:269856 )

• increase heart weight-to-body weight ratios

• increase in heart weight is caused by atrial thrombi

• however, ventricle weight is not altered

cardiac hypertrophy ( J:269856 )

• hearts show increased expression of cardiac hypertrophy markers at 12 and 20 months of age but not a 4 weeks of age

• hearts of 12 week old mice show a hypertrophic phenotype, indicating that concentric hypertrophy transiently proceeds prior to dilated cardiomyopathy

dilated heart ( J:269856 )

• cardiac dilatation

dilated heart left ventricle ( J:269856 )

dilated cardiomyopathy ( J:269856 )

• hearts show features of dilated cardiomyopathy, including enlarged ventricular cavities with thin walls and reactive myocardial fibrosis

decreased cardiac muscle contractility ( J:269856 )

• diminished ejection fraction and fractional shortening

abnormal heart echocardiography feature ( J:269856 )

• echocardiography indicates severe dilatation of the left ventricle, decreased contractility without alteration in heart rate, diminished ejection fraction and fractional shortening, and enlarged left ventricular end-systolic dimensions and end-diastolic dimensions at 4 months of age

cellular

decreased mitochondrial number ( J:269856 )

• hearts show a decrease in the number of mitochondria

homeostasis/metabolism

abnormal atrial thrombosis ( J:269856 )

• atrial thrombi

abnormal lipid level ( J:269856 )

• cardiac lipid accumulation

muscle

dilated cardiomyopathy ( J:269856 )

• hearts show features of dilated cardiomyopathy, including enlarged ventricular cavities with thin walls and reactive myocardial fibrosis

decreased cardiac muscle contractility ( J:269856 )

• diminished ejection fraction and fractional shortening

abnormal sarcomere morphology ( J:269856 )

• disarray of sarcomeres in hearts

growth/size/body

increased heart weight ( J:269856 )

• increase heart weight-to-body weight ratios

• increase in heart weight is caused by atrial thrombi

• however, ventricle weight is not altered

cardiac hypertrophy ( J:269856 )

• hearts show increased expression of cardiac hypertrophy markers at 12 and 20 months of age but not a 4 weeks of age

• hearts of 12 week old mice show a hypertrophic phenotype, indicating that concentric hypertrophy transiently proceeds prior to dilated cardiomyopathy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:269856

Genotype
MGI:6276352

cn22

• Allelic Composition: Ncoa6^tm1Jkr/Ncoa6⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

cardiovascular system

dilated cardiomyopathy ( J:269856 )

• mice exhibit characteristics of dilated cardiomyopathy with late onset

decreased cardiac muscle contractility ( J:269856 )

• decrease in percent fractional shortening

abnormal heart echocardiography feature ( J:269856 )

• echocardiography indicates decreased fractional shortening and enlarged left ventricular end-systolic dimensions and end-diastolic dimensions

muscle

dilated cardiomyopathy ( J:269856 )

• mice exhibit characteristics of dilated cardiomyopathy with late onset

decreased cardiac muscle contractility ( J:269856 )

• decrease in percent fractional shortening

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:269856

Genotype
MGI:5911326

cn23

• Allelic Composition: Med1^tm2Jkr/Med1^tm2Jkr; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

Heart sections of Med1^tm2Jkr/Med1^tm2Jkr Tg(Myh6-cre)2182Mds/0 heart reveal thinning of ventricular walls and dilation of chambers.

mortality/aging

premature death ( J:243730 )

• nearly 100% of mice die within 10 days post weaning

cardiovascular system

abnormal myocardial fiber morphology ( J:243730 )

• lipid vacuoles of differing sizes are seen in cardiomyocytes

• cardiomyocytes show varying mitochondrial abnormalities, with some mitochondria containing lipid droplets and membranous swirls

decreased myocardial fiber mitochondrial DNA content ( J:243730 )

• mitochondrial DNA content is decreased in hearts

dilated heart atrium ( J:243730 )

enlarged heart ( J:243730 )

• size of the heart increases by 22-29 days of age

thin ventricular wall ( J:243730 )

dilated heart ventricle ( J:243730 )

• dilation of right and left ventricular chambers with thinning of the walls and myocardial cells

cardiac interstitial fibrosis ( J:243730 )

dilated cardiomyopathy ( J:243730 )

• dilated cardiomyopathy with atrial and ventricular dilatation

decreased cardiac muscle contractility ( J:243730 )

• at day 29, contractility of heart is diminished with a fractional shortening of 9.47% compared to 41.08% in controls and ejection fraction of 20.7% compared to 74.27% in controls

abnormal heart echocardiography feature ( J:243730 )

• echocardiography shows increased left ventricular end-diastolic internal dimension, decreased fractional shortening, and decreased ejection fraction

congestive heart failure ( J:243730 )

cellular

decreased myocardial fiber mitochondrial DNA content ( J:243730 )

• mitochondrial DNA content is decreased in hearts

cardiac interstitial fibrosis ( J:243730 )

increased cardiomyocyte apoptosis ( J:243730 )

• increase in apoptosis in hearts, with an increase in the percentage of apoptotic cardiomyocytes

homeostasis/metabolism

cardiac edema ( J:243730 )

• heart weight/body weight ratio is increased but dry heart weight is decreased, suggesting edematous heart

pulmonary edema ( J:243730 )

• lung weight/body weight ratio is increased most likely due to pulmonary edema

muscle

abnormal myocardial fiber morphology ( J:243730 )

• lipid vacuoles of differing sizes are seen in cardiomyocytes

• cardiomyocytes show varying mitochondrial abnormalities, with some mitochondria containing lipid droplets and membranous swirls

decreased myocardial fiber mitochondrial DNA content ( J:243730 )

• mitochondrial DNA content is decreased in hearts

dilated cardiomyopathy ( J:243730 )

• dilated cardiomyopathy with atrial and ventricular dilatation

decreased cardiac muscle contractility ( J:243730 )

• at day 29, contractility of heart is diminished with a fractional shortening of 9.47% compared to 41.08% in controls and ejection fraction of 20.7% compared to 74.27% in controls

increased cardiomyocyte apoptosis ( J:243730 )

• increase in apoptosis in hearts, with an increase in the percentage of apoptotic cardiomyocytes

abnormal Z line morphology ( J:243730 )

• irregularities in Z band pattern

respiratory system

pulmonary edema ( J:243730 )

• lung weight/body weight ratio is increased most likely due to pulmonary edema

growth/size/body

enlarged heart ( J:243730 )

• size of the heart increases by 22-29 days of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:243730
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:243730

Genotype
MGI:3851401

cn24

• Allelic Composition: Zfpm2^tm1Sho/Zfpm2^tm2Sho; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

Dilated cardiomyopathy in Zfpm2^tm1Sho/Zfpm2^tm2Sho Tg(Myh6-cre)2182Mds/0 mice

mortality/aging

premature death ( J:150452 )

• mice survive normally to weaning but die at 8-12 weeks

postnatal lethality, complete penetrance ( J:150452 )

cardiovascular system

cardiovascular system phenotype ( J:150452 )

N • at E14.5 no structural heart defects or coronary vascular plexus abnormalities are observed

N • myocardium thickens normally and contains normal number of intramyocardial vessels

abnormal cardiovascular development ( J:150452 )

• decreased coronary vasculature is observed in adults

• density of PECAM positive vessels particularly capillaries are reduced in density; coronary arteriole density is also decreased

cardiac fibrosis ( J:150452 )

• significantly increased and replaces apoptotic tissues

dilated heart ( J:150452 )

• adult hearts are dilated

dilated heart ventricle ( J:150452 )

• ventricular dilation is observed

abnormal coronary circulation ( J:150452 )

• decreased myocardial perfusion is observed in adults, resulting in tissue hypoxia

decreased cardiac muscle contractility ( J:150452 )

• fractional shortening is severely depressed in adults

decreased heart ventricle muscle contractility ( J:150452 )

• contraction is depressed in adults

muscle

decreased cardiac muscle contractility ( J:150452 )

• fractional shortening is severely depressed in adults

decreased heart ventricle muscle contractility ( J:150452 )

• contraction is depressed in adults

increased cardiomyocyte apoptosis ( J:150452 )

• significantly increased in adult heart compared to controls

cellular

increased cardiomyocyte apoptosis ( J:150452 )

• significantly increased in adult heart compared to controls

Genotype
MGI:7544914

cn25

• Allelic Composition: Gt(ROSA)26Sor^tm2(Mib1)Jlp/Gt(ROSA)26Sor⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

cardiovascular system

cardiovascular system phenotype ( J:338889 )

N • normal hearts in E15.5 embryos

Genotype
MGI:7544917

cn26

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Mib1*V943F)Jlp}/Gt(ROSA)26Sor⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

cardiovascular system

abnormal heart ventricle morphology ( J:338889 )

• noncompacted trabeculae in ventricular myocardium in E15.5 embryos

thin ventricle myocardium compact layer ( J:338889 )

• in E15.5 embryos

• reduced compact-to-trabecular myocardium ratio in E15.5 embryos

muscle

thin ventricle myocardium compact layer ( J:338889 )

• in E15.5 embryos

• reduced compact-to-trabecular myocardium ratio in E15.5 embryos

Genotype
MGI:3687001

cn27

• Allelic Composition: Npr1^tm1Kuhn/Npr1^tm1Kuhn; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

cardiovascular system

abnormal myocardial fiber morphology ( J:83298 )

• conditional mutants exhibit significantly increased ventricular cardiomyocyte diameters relative to homozygous Npr1^tm1Kuhn mice, in the absence of interstitial fibrosis

cardiac hypertrophy ( J:83298 )

• conditional mutants show a significant increase in the heart weight (HW) to body weight (BW) ratio relative to homozygous Npr1^tm1Kuhn mice

• under baseline conditions, cardiac ventricles from conditional mutants show elevated expression levels of cardiac hypertrophy genes ANP, alpha-skeletal-actin, and beta-MHC (~4.9-fold, ~1.7-fold, and ~2-fold, respectively); the beta-MHC/alpha-MHC ratio is increased by ~2.7-fold

• in response to pressure overload induced by transverse aortic constriction (TAC), conditional mutants show an enhanced cardiac hypertrophic response, with a significantly lower SBP and induced pressure gradient, a greater LVW/BW index but a similar mortality rate relative to homozygous Npr1^tm1Kuhn mice

cardiac interstitial fibrosis ( J:83298 )

• in response to pressure overload induced by TAC, conditional mutants show a slight increase in cardiac interstitial fibrosis relative to homozygous Npr1^tm1Kuhn mice (24% vs 8%, respectively)

abnormal cardiac muscle relaxation ( J:83298 )

• conditional mutants show normal heart rates and left ventricular contractility relative to homozygous Npr1^tm1Kuhn mice; in addition, chronotropic and inotropic responses to the beta-agonist dobutamine are preserved with no signs of cardiac dysfunction

• in contrast, baseline maximal relaxation rates and the lusitropic responses to low levels of beta-adrenergic stimulation are significantly reduced

decreased systemic arterial systolic blood pressure ( J:83298 )

• conditional mutants display slightly but significantly lower SBP relative to age- and sex-matched homozygous Npr1^tm1Kuhn mice, by ~7-10 mmHg

hypotension ( J:83298 )

• surprisingly, conditional mutants exhibit a mild but significant arterial hypotension by 7-10 mmHg

congestive heart failure ( J:83298 )

• in response to TAC-induced pressure load, conditional mutants display significant deterioration of cardiac function relative to TAC-operated homozygous Npr1^tm1Kuhn mice

• at 10-14 days after TAC, conditional mutants show decreased LV contractility and relaxation as well as increased LV end-diastolic pressure and greater ratios of lung weight (LW) and right ventricular weight (RVW) to BW, indicating congestive heart failure without clinical signs of RV failure

muscle

abnormal myocardial fiber morphology ( J:83298 )

• conditional mutants exhibit significantly increased ventricular cardiomyocyte diameters relative to homozygous Npr1^tm1Kuhn mice, in the absence of interstitial fibrosis

abnormal cardiac muscle relaxation ( J:83298 )

• conditional mutants show normal heart rates and left ventricular contractility relative to homozygous Npr1^tm1Kuhn mice; in addition, chronotropic and inotropic responses to the beta-agonist dobutamine are preserved with no signs of cardiac dysfunction

• in contrast, baseline maximal relaxation rates and the lusitropic responses to low levels of beta-adrenergic stimulation are significantly reduced

homeostasis/metabolism

increased circulating atrial natriuretic factor ( J:83298 )

• conditional mutants exhibit a >2-fold increase in plasma ANP levels relative to homozygous Npr1^tm1Kuhn mice

growth/size/body

cardiac hypertrophy ( J:83298 )

• conditional mutants show a significant increase in the heart weight (HW) to body weight (BW) ratio relative to homozygous Npr1^tm1Kuhn mice

• under baseline conditions, cardiac ventricles from conditional mutants show elevated expression levels of cardiac hypertrophy genes ANP, alpha-skeletal-actin, and beta-MHC (~4.9-fold, ~1.7-fold, and ~2-fold, respectively); the beta-MHC/alpha-MHC ratio is increased by ~2.7-fold

• in response to pressure overload induced by transverse aortic constriction (TAC), conditional mutants show an enhanced cardiac hypertrophic response, with a significantly lower SBP and induced pressure gradient, a greater LVW/BW index but a similar mortality rate relative to homozygous Npr1^tm1Kuhn mice

cellular

cardiac interstitial fibrosis ( J:83298 )

• in response to pressure overload induced by TAC, conditional mutants show a slight increase in cardiac interstitial fibrosis relative to homozygous Npr1^tm1Kuhn mice (24% vs 8%, respectively)

Genotype
MGI:3721269

cn28

• Allelic Composition: Gab1^tm1Nmoc/Gab1^tm1Nmoc; Gab2^tm1Thir/Gab2^tm1Thir; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

premature death ( J:124033 )

• 70% of mice die between 3 and 72 weeks due to heart failure

cardiovascular system

abnormal heart morphology ( J:124033 )

• sarcomere length in the heart is reduced

abnormal endocardium morphology ( J:124033 )

• after 3 weeks, deposits of elastic fibers and collagen in the endocardium are observed

thin interventricular septum ( J:124033 )

• at 10 weeks, the interventricular septal wall is thinned

increased heart weight ( J:124033 )

• mice have a higher heart weight-to-body weight ratio when compared to control mice

• both the left and right ventricle are enlarged

abnormal heart left ventricle morphology ( J:124033 )

• vessels in the left ventricle are abnormally dilated and are impaired in the recruitment of vascular smooth muscle cells

dilated heart ( J:124033 )

• mice that die of heart failure exhibit dilation of heart ventricles

decreased cardiac muscle contractility ( J:124033 )

• decrease in fractional shortening at 10 weeks of age

abnormal cardiac muscle relaxation ( J:124033 )

• left ventricle relaxation is impaired

increased left ventricle diastolic pressure ( J:124033 )

• at 10 weeks, the left ventricle end-diastolic dimension is increased and accompanied by decreased fractional shortening

congestive heart failure ( J:124033 )

• 70% of mice die between 3 and 72 weeks due to heart failure

muscle

decreased cardiac muscle contractility ( J:124033 )

• decrease in fractional shortening at 10 weeks of age

abnormal cardiac muscle relaxation ( J:124033 )

• left ventricle relaxation is impaired

growth/size/body

increased heart weight ( J:124033 )

• mice have a higher heart weight-to-body weight ratio when compared to control mice

• both the left and right ventricle are enlarged

Genotype
MGI:3717096

cn29

• Allelic Composition: Shc1^tm8Paw/Shc1^tm9.1Paw; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:122927 )

• between E12.5 and 13.5, 8/19 mutant embryos are dead, compared to all mutant embryos not expressing the cre-recombined allele; remaining embryos have regularly beating hearts and normal-appearing trabeculae

Genotype
MGI:3711512

cn30

• Allelic Composition: Cxadr^tm1Mds/Cxadr^tm1.1Mds; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

mortality/aging

mortality/aging ( J:121400 )

N • many conditional null mice are born alive and survive to adulthood (20/102)

cardiovascular system

abnormal sinoatrial valve morphology ( J:121400 )

• sinuatrial valves show mild abnormalities in embryos, with only 1 embryo showing absence or attenuation comparable to constitutive null mice

abnormal heart ventricle morphology ( J:121400 )

• embryos show only mild or no abnormal ventricular thickening with little or no increase in proliferating cells

Genotype
MGI:3711507

cn31

• Allelic Composition: Cxadr^tm1Mds/Cxadr^tm1Mds; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

mortality/aging

mortality/aging ( J:121400 )

N • many conditional null mice are born alive and survive to adulthood (20/102)

cardiovascular system

abnormal sinoatrial valve morphology ( J:121400 )

• sinuatrial valves show mild abnormalities in embryos, with only 1 embryo showing absence or attenuation comparable to constitutive null mice

abnormal heart ventricle morphology ( J:121400 )

• embryos show only mild or no abnormal ventricular thickening with little or no increase in proliferating cells

Genotype
MGI:3689723

cn32

• Allelic Composition: Jarid2^tm1Yskl/Jarid2^tm1Yskl; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

normal phenotype

no abnormal phenotype detected ( J:114450 )

• mice display no lethality up to 21 days after birth (P21); no detailed analyses have been done

Genotype
MGI:3697609

cn33

• Allelic Composition: Acvr1^tm1Vk/Acvr1^tm1.1Vk; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:103532 )

N • mutants are viable and fail to display any detectable altered cardiac phenotype

Genotype
MGI:4879018

cn34

• Allelic Composition: Stat3^tm1Xyfu/Stat3^tm1.1Xyfu; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * FVB/N

cardiovascular system

enlarged heart ( J:86400 )

• after 6 months of age

increased heart left ventricle size ( J:86400 )

• at 200 days, mice exhibit increased left ventricular chamber size compared with wild-type mice

cardiac fibrosis ( J:86400 )

• mild at 6 months

• severe at 9 months

dilated heart ( J:86400 )

• after 6 months of age

abnormal cardiovascular system physiology ( J:86400 )

• doxorubicin-treated mice exhibit a greater decrease in cardiac systolic function compared with similarly treated wild-type mice

decreased cardiac muscle contractility ( J:86400 )

• at 200 days

congestive heart failure ( J:86400 )

• after 6 months of age

immune system

increased tumor necrosis factor secretion ( J:86400 )

• in the cardiac myocytes of LPS-treated mice

increased susceptibility to endotoxin shock ( J:86400 )

• LPS-treated mice exhibit increased myocyte apoptosis and TNF-alpha levels in cardiac myocytes compared with similarly treated wild-type mice

homeostasis/metabolism

ascites ( J:86400 )

• after 6 months of age

increased physiological sensitivity to xenobiotic ( J:86400 )

• doxorubicin-treated mice exhibit a greater decrease in cardiac systolic function compared with similarly treated wild-type mice

respiratory system

respiratory distress ( J:86400 )

• after 6 months of age

growth/size/body

enlarged heart ( J:86400 )

• after 6 months of age

cachexia ( J:86400 )

• after 6 months of age

muscle

decreased cardiac muscle contractility ( J:86400 )

• at 200 days

increased cardiomyocyte apoptosis ( J:86400 )

• LPS-treated mice exhibit increased myocyte apoptosis compared with similarly treated wild-type mice

cellular

increased cardiomyocyte apoptosis ( J:86400 )

• LPS-treated mice exhibit increased myocyte apoptosis compared with similarly treated wild-type mice

Genotype
MGI:4879021

cn35

• Allelic Composition: Stat3^tm1Xyfu/Stat3⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * FVB/N

immune system

increased tumor necrosis factor secretion ( J:86400 )

• in the cardiac myocytes of LPS-treated mice

increased susceptibility to endotoxin shock ( J:86400 )

• LPS-treated mice exhibit increased TNF-alpha levels in cardiac myocytes compared with similarly treated wild-type mice although not as severely as in homozygous mice

cardiovascular system

cardiac fibrosis ( J:86400 )

• severe at 9 months

Genotype
MGI:5907132

cn36

• Allelic Composition: Mdm4^tm2Glo/Mdm4^tm2.1Glo; Tg(Myh6-cre)2182Mds/0; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N

mortality/aging

extended life span ( J:137114 )

• mice show an extended median survival of 274 days compared to compound heterozygous Mdm4^tm2Glo/Mdm4^tm2.1Glo conditional mutants

Genotype
MGI:3616710

cn37

• Allelic Composition: Mdm2^tm1Glo/Mdm2^tm2.1Glo; Tg(Myh6-cre)2182Mds/0; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:104114 )

N • exhibit rescue of the heart lethality seen in conditional Mdm2 mice and have the same life span as single homozygous Trp53 mice

Genotype
MGI:3807709

cn38

• Allelic Composition: Gja1^tm8Kwi/Gja1⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S2/SvPas * FVB/N

mortality/aging

premature death ( J:132032 )

• mutants are born live die during initial 6.5 months after birth

lethality throughout fetal growth and development, incomplete penetrance ( J:132032 )

• 44% lethality occurs between E14.5 and 16.5

cardiovascular system

cardiovascular system phenotype ( J:132032 )

N • mice do not differ significantly from wild-type in left ventricular (lv) muscle mass, lv end-diastolic volume and lv ejection fraction

N • postnatally, mice do not differ significantly from wild-type in left ventricular (lv) muscle mass, lv end-diastolic volume and lv ejection fraction

ventricular tachycardia ( J:132032 )

• cardiac arrythmias are observed are observed after excorporation for ex vivo cardiac functional analyses including spontaneous and sustained ventricular tachycardias

irregular heartbeat ( J:132032 )

• cardiac arrythmias are observed are observed after excorporation for ex vivo cardiac functional analyses including spontaneous and sustained ventricular tachycardias

• in vivo, spontaneous arrhythmic events such as ventricular extra systole (VES) are observed; frequency and severity of such events increase with by hypoxic stimulation

abnormal heart electrocardiography waveform feature ( J:132032 )

• surface and intercardiac ECGs ex vivo show a broadening of the QRS complex and decrease in the R wave in ventricle activity indicating disturbed impulse propagation

prolonged QRS complex duration ( J:132032 )

abnormal R wave ( J:132032 )

• decrease in the R wave

abnormal myocardial fiber physiology ( J:132032 )

• isolated fetal cardiomyocytes show a 1.6-fold higher beating frequency than wild-type cells

Genotype
MGI:6098758

cn39

• Allelic Composition: Mecp2^tm1Jae/Y; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * FVB/N

behavior/neurological

behavior/neurological phenotype ( J:241788 )

♂N • mice show no differences in activity in either the light or dark phases

cardiovascular system

cardiovascular system phenotype ( J:241788 )

♂N • mice do not exhibit an increase in sinus pauses, premature ventricular contractions, atrioventricular block, or nonsustained ventricular tachycardia, and do not show QT prolongation or increased susceptibility to induced arrhythmias

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:241788 )

♂N • mice show no changes in temperature in either the light or dark phases

Genotype
MGI:5297552

cn40

• Allelic Composition: Fstl1^tm1.1Mvdh/Fstl1^tm1.1Mvdh; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB/N

cardiovascular system

pulmonary vascular congestion ( J:177416 )

• following pressure overload

decreased angiogenesis ( J:177416 )

• following pressure overload, the increase in myocardial capillary density is less than in wild-type mice

increased myocardial fiber size ( J:177416 )

• following pressure overload

abnormal coronary vessel morphology ( J:177416 )

• following pressure overload, the increase in myocardial capillary density is less than in wild-type mice

abnormal heart septum morphology ( J:177416 )

• increased thickness following pressure overload

increased heart weight ( J:177416 )

• following pressure overload

cardiac hypertrophy ( J:177416 )

• following pressure overload

increased heart left ventricle size ( J:177416 )

• increased left ventricular wall thickness following pressure overload

increased heart left ventricle weight ( J:177416 )

• following pressure overload

cardiac fibrosis ( J:177416 )

• following pressure overload

decreased heart left ventricle muscle contractility ( J:177416 )

• increased left ventricular dimension and reduced fractional shortening following pressure overload

increased response of heart to induced stress ( J:177416 )

• following pressure overload, mice exhibit exacerbated cardiac myocyte hypertrophy and dysfunction compared with similarly treated wild-type mice

homeostasis/metabolism

increased response of heart to induced stress ( J:177416 )

• following pressure overload, mice exhibit exacerbated cardiac myocyte hypertrophy and dysfunction compared with similarly treated wild-type mice

muscle

increased myocardial fiber size ( J:177416 )

• following pressure overload

decreased heart left ventricle muscle contractility ( J:177416 )

• increased left ventricular dimension and reduced fractional shortening following pressure overload

respiratory system

pulmonary vascular congestion ( J:177416 )

• following pressure overload

growth/size/body

increased heart weight ( J:177416 )

• following pressure overload

cardiac hypertrophy ( J:177416 )

• following pressure overload

Genotype
MGI:6705053

cn41

• Allelic Composition: Ddt^tm1Lhy/Ddt^tm1Lhy; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:213776 )

N • mice exhibit normal baseline cardiac morphology and histology, with intact left ventricle size, wall thickness, and ejection fraction, and normal left ventricle contractile function ex vivo

cardiac muscle necrosis ( J:213776 )

• hearts exposed to ischemia-reperfusion exhibit 2.3-fold more necrosis than controls

• mice subjected to transient left coronary artery ligation followed by reperfusion show a 3.5-fold greater necrosis in the left ventricle

decreased heart left ventricle muscle contractility ( J:213776 )

• left ventricle fractional shortening is 50% lower than in controls after ischemia-reperfusion

increased susceptibility to myocardial ischemic injury ( J:213776 )

• hearts exposed to ischemia-reperfusion show exacerbated left ventricle contractile dysfunction, with less recovery of the left ventricular developed pressure-heart rate index and other parameters of left ventricle contractile function, and increase in necrosis

• mice subjected to transient left coronary artery ligation followed by reperfusion show more severe cardiac injury than controls, with 3.5-fold greater necrosis in left ventricle and 2.5-fold higher serum troponin release

• recovery of contractile function and extent of injury after ischemia-reperfusion is similar to wild-type mice after perfusion with recombinant DTT

increased myocardial infarct size ( J:213776 )

• infract size is greater in isolated perfused hearts during reperfusion after ischemia than in wild-type hearts

homeostasis/metabolism

increased susceptibility to myocardial ischemic injury ( J:213776 )

• hearts exposed to ischemia-reperfusion show exacerbated left ventricle contractile dysfunction, with less recovery of the left ventricular developed pressure-heart rate index and other parameters of left ventricle contractile function, and increase in necrosis

• mice subjected to transient left coronary artery ligation followed by reperfusion show more severe cardiac injury than controls, with 3.5-fold greater necrosis in left ventricle and 2.5-fold higher serum troponin release

• recovery of contractile function and extent of injury after ischemia-reperfusion is similar to wild-type mice after perfusion with recombinant DTT

increased myocardial infarct size ( J:213776 )

• infract size is greater in isolated perfused hearts during reperfusion after ischemia than in wild-type hearts

muscle

cardiac muscle necrosis ( J:213776 )

• hearts exposed to ischemia-reperfusion exhibit 2.3-fold more necrosis than controls

• mice subjected to transient left coronary artery ligation followed by reperfusion show a 3.5-fold greater necrosis in the left ventricle

decreased heart left ventricle muscle contractility ( J:213776 )

• left ventricle fractional shortening is 50% lower than in controls after ischemia-reperfusion

Genotype
MGI:5304714

cn42

• Allelic Composition: Vhl^tm1Jae/Vhl^tm1Jae; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

mortality/aging

premature death ( J:179490 )

• mean survival is 9 weeks

postnatal lethality, complete penetrance ( J:193425 )

• die between P16 and P18 due to sudden cardiac death

cardiovascular system

increased angiogenesis ( J:179490 )

increased heart weight ( J:179490 )

• at 5 weeks and severe at 8 weeks

abnormal heart left ventricle morphology ( J:179490 )

• at 8 weeks, mice exhibit reduced left ventricular wall thickness and increased left ventricular end-diastolic dimension compared with control mice

decreased heart ventricle muscle contractility ( J:179490 )

• at 5 weeks and severe at 8 weeks

decreased heart rate ( J:193425 )

• neonates exhibit decreased heart rate at 10 days after birth

irregular heartbeat ( J:193425 )

• neonates exhibit frequent cardiac arrhythmia, consistent with sudden cardiac death

prolonged QRS complex duration ( J:193425 )

• neonates exhibit increased QRS at 10 days after birth

prolonged QT interval ( J:193425 )

• exhibit increased QTc (c denotes correction for heart rate) and QTc dispersion at 10 days after birth

cardiomyopathy ( J:179490 )

• severe at 8 weeks of age

muscle

decreased heart ventricle muscle contractility ( J:179490 )

• at 5 weeks and severe at 8 weeks

cardiomyopathy ( J:179490 )

• severe at 8 weeks of age

cellular

decreased mitochondrial number ( J:179490 )

• myocytes exhibit mitochondrial loss

growth/size/body

increased heart weight ( J:179490 )

• at 5 weeks and severe at 8 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sudden infant death syndrome		DOID:9007	OMIM:272120	J:193425

Genotype
MGI:3613580

cn43

• Allelic Composition: Mef2c^tm1Eno/Mef2c^tm1Jjs; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * 129S7/SvEvBrd * FVB/N

normal phenotype

no abnormal phenotype detected ( J:100949 )

• no defects in heart or body weight parameters or in electrocardiogram analyses are seen in mice between 14 and 40 weeks of age

• suggests that this gene is not required for development or function of the heart after the looping morphogenesis stage

Genotype
MGI:3616711

cn44

• Allelic Composition: Mdm4^tm2Glo/Mdm4^tm2.1Glo; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N

mortality/aging

premature death ( J:104114 , J:137114 )

• some mice die within 1 year for unknown reasons, however do not observe any embryonic lethality (J:104114)

• median survival of 208 and 243 days for males and females, respectively (J:137114)

• mice die as a result of heart failure (J:137114)

cellular

increased cardiomyocyte apoptosis ( J:137114 )

cardiovascular system

cardiovascular system phenotype ( J:104114 )

N • no abnormalities in embryonic hearts are seen

decreased myocardial fiber number ( J:137114 )

• hearts exhibit half the number of cardiomyocytes at 8 months of age

increased myocardial fiber size ( J:137114 )

• marker analysis indicates cardiomyocyte hypertrophy

enlarged heart ( J:137114 )

thin ventricular wall ( J:137114 )

• ventricular walls are thinner and hypertrophic

dilated heart ventricle ( J:137114 )

• all 4 chambers are dilated and paler than control hearts

cardiac fibrosis ( J:137114 )

dilated cardiomyopathy ( J:137114 )

• severe dilated cardiomyopathy

congestive heart failure ( J:137114 )

• by 8-10 months of age, most mice have swollen bodies, have difficulty moving, and are out of breath

homeostasis/metabolism

edema ( J:137114 )

• edema in the lung and/or abdomen

muscle

decreased myocardial fiber number ( J:137114 )

• hearts exhibit half the number of cardiomyocytes at 8 months of age

increased myocardial fiber size ( J:137114 )

• marker analysis indicates cardiomyocyte hypertrophy

dilated cardiomyopathy ( J:137114 )

• severe dilated cardiomyopathy

increased cardiomyocyte apoptosis ( J:137114 )

growth/size/body

enlarged heart ( J:137114 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:137114

Genotype
MGI:6303767

cn45

• Allelic Composition: Bdh1^{tm1c(EUCOMM)Wtsi}/Bdh1^{tm1c(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:274475 )

• slightly fewer than expected mice are present at weaning

cardiovascular system

abnormal heart left ventricle morphology ( J:274475 )

• fasted mice exhibit increased left ventricular internal diameter and volume compared with control mice

• however, mice exhibit normal cardiac phenotype under basal conditions

decreased heart left ventricle muscle contractility ( J:274475 )

• fasted mice exhibit reduced left ventricular fractional shortening and longitudinal strain rate compared with control mice

• 4 weeks after pressure overload induced by transverse aortic constriction combined with a small apical myocardial infarction (TAC/MI), mice exhibit more severe left ventricle dysfunction including lower left ventricle ejection fraction and greater left ventricle end-diastolic volume and end-systolic volume compared with control mice

muscle

decreased heart left ventricle muscle contractility ( J:274475 )

• fasted mice exhibit reduced left ventricular fractional shortening and longitudinal strain rate compared with control mice

• 4 weeks after pressure overload induced by transverse aortic constriction combined with a small apical myocardial infarction (TAC/MI), mice exhibit more severe left ventricle dysfunction including lower left ventricle ejection fraction and greater left ventricle end-diastolic volume and end-systolic volume compared with control mice

Genotype
MGI:5582621

cn46

• Allelic Composition: Grk5^tm2Rjl/Grk5^tm2Rjl; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6J * FVB/N

cardiovascular system

cardiac hypertrophy ( J:212635 )

• 12 weeks after transaortic constriction, mice exhibit attenuated cardiac hypertrophy compared with wild-type mice

decreased response of heart to induced stress ( J:212635 )

• 12 weeks after transaortic constriction, mice exhibit attenuated cardiac hypertrophy with no increase in left ventricular dilatation and no change in ejection fraction compared with wild-type mice

homeostasis/metabolism

decreased response of heart to induced stress ( J:212635 )

• 12 weeks after transaortic constriction, mice exhibit attenuated cardiac hypertrophy with no increase in left ventricular dilatation and no change in ejection fraction compared with wild-type mice

growth/size/body

cardiac hypertrophy ( J:212635 )

• 12 weeks after transaortic constriction, mice exhibit attenuated cardiac hypertrophy compared with wild-type mice

Genotype
MGI:5829559

cn47

• Allelic Composition: Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJaeSor * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:223139 )

• although born at normal Mendelian ratios, all mice die abruptly from heart failure at exactly 10 days after birth

cardiovascular system

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy

congestive heart failure ( J:223139 )

muscle

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy

Genotype
MGI:3851413

cn48

• Allelic Composition: Gata4^tm1Sho/Gata4⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac

cardiovascular system

cardiovascular system phenotype ( J:150452 )

N • animals show normal development

Genotype
MGI:3851409

cn49

• Allelic Composition: Gata4^tm1Sho/Gata4^tm1.1Wtp; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd

Reduced coronary microvasculature, decreased capillary density and increased fibrosis in Gata4^tm1.1Wtp/Gata4^tm1Sho Tg(Myh6-cre)2182Mds/0 hearts

cardiovascular system

dilated heart ventricle ( J:150452 )

• ventricular dilation is observed

abnormal cardiovascular system physiology ( J:150452 )

• severely diminished systolic function at 8-14 weeks

Genotype
MGI:5905569

cn50

• Allelic Composition: Esrrb^tm1.1Nat/Esrrb^tm1.1Nat; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * FVB/N

mortality/aging

premature death ( J:241078 )

• poor survival rates after 9-10 months of age

cardiovascular system

enlarged heart ( J:241078 )

• increase in heart weight to body weight and heart weight to tibial length ratios

dilated heart left ventricle ( J:241078 )

cardiac fibrosis ( J:241078 )

• increase in fibrosis in the left ventricle

dilated cardiomyopathy ( J:241078 )

• mice develop adult-onset dilated cardiomyopathy associated with a decrease in anterior wall thickness, increased left ventricular end systolic diameter and left ventricular end diastolic diameter and a 60% decrease in fractional shortening

decreased cardiac muscle contractility ( J:241078 )

• decrease in cardiac function at 9 months of age but not at 4 and 6 months, with a 60% decrease in fractional shortening

decreased heart ventricle muscle contractility ( J:241078 )

• ventricular cardiomyocytes exhibit impaired contractility and show a decrease in both contractile distance (sarcomere shortening) and speed of contraction at 6 and 9 months of age

abnormal myocardial fiber physiology ( J:241078 )

• ventricular cardiomyocytes exhibit impaired calcium handling and deregulation of the excitation-contraction coupling apparatus

decreased calcium uptake by cardiac muscle ( J:241078 )

• ventricular cardiomyocytes exhibit decreased calcium release and a trend towards decreased calcium uptake as early as 4 months of age

increased calcium uptake by cardiac muscle ( J:241078 )

• by 6 months of age, calcium release and uptake by ventricular cardiomyocytes are increased and this persists at 9 months

• increase in calcium transients at 6 and 9 months of age

congestive heart failure ( J:241078 )

• expression analysis indicates a heart failure gene signature in hearts

muscle

dilated cardiomyopathy ( J:241078 )

• mice develop adult-onset dilated cardiomyopathy associated with a decrease in anterior wall thickness, increased left ventricular end systolic diameter and left ventricular end diastolic diameter and a 60% decrease in fractional shortening

decreased cardiac muscle contractility ( J:241078 )

• decrease in cardiac function at 9 months of age but not at 4 and 6 months, with a 60% decrease in fractional shortening

decreased heart ventricle muscle contractility ( J:241078 )

• ventricular cardiomyocytes exhibit impaired contractility and show a decrease in both contractile distance (sarcomere shortening) and speed of contraction at 6 and 9 months of age

abnormal sarcomere morphology ( J:241078 )

• ventricular cardiomyocytes exhibit an increase in sarcomere length only after 9 months of age

growth/size/body

enlarged heart ( J:241078 )

• increase in heart weight to body weight and heart weight to tibial length ratios

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:241078

Genotype
MGI:3840255

cn51

• Allelic Composition: Ptpn11^tm6Bgn/Ptpn11⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:147154 )

N • no gross cardiac defects are seen

Genotype
MGI:2687389

cn52

• Allelic Composition: Ednra^tm2Ywa/Ednra^tm2Ywa; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

normal phenotype

no abnormal phenotype detected ( J:86476 )

• mutant mice are born at the expected Mendelian frequency and survive to adulthood in the absence of health problems

• at 6 weeks of age, mutants exhibit normal cardiac anatomy and weight, with no significant changes in histology of the right and left ventricular wall and interventricular septum relative to control mice

• when subjected to echocardiography, anesthetized 10-week-old male mutants exhibit normal cardiac contractility (as measured by peak velocity of left outflow tract (Vp), aortic velocity time integral, ejection time, and heart rate) relative to control mice

• surprisingly, in response to cardiac stress induced by 10-day infusion of angiotensin II or isoproterenol, male mutants display hypertrophic and contractile responses similar to those observed in control mice

Genotype
MGI:4946095

cn53

• Allelic Composition: Myh10^tm7Rsad/Myh10^tm7Rsad; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

cardiovascular system

abnormal intercalated disk morphology ( J:170148 )

• widened and distorted in 4 of 5 mice

increased myocardial fiber size ( J:170148 )

• at P0, 6 months, and 10 months with abnormal nuclei

ventricular septal defect ( J:170148 )

• in 2 of 9 mice without double outlet heart right ventricle

cardiac interstitial fibrosis ( J:170148 )

• at 10 months

decreased cardiac muscle contractility ( J:170148 )

• at 10 months

abnormal impulse conducting system conduction ( J:170148 )

cardiomyopathy ( J:170148 )

• at 10 months, mice exhibit increased left ventricular internal diameter at the end of systole and decreased fractional shortening with abnormal intercalated disc compared with wild-type mice

heart inflammation ( J:170148 )

• at 6 and 10 months

homeostasis/metabolism

abnormal atrial thrombosis ( J:170148 )

• in the atrium of 2 in 8 mice at 10 months

immune system

heart inflammation ( J:170148 )

• at 6 and 10 months

muscle

abnormal intercalated disk morphology ( J:170148 )

• widened and distorted in 4 of 5 mice

increased myocardial fiber size ( J:170148 )

• at P0, 6 months, and 10 months with abnormal nuclei

decreased cardiac muscle contractility ( J:170148 )

• at 10 months

cardiomyopathy ( J:170148 )

• at 10 months, mice exhibit increased left ventricular internal diameter at the end of systole and decreased fractional shortening with abnormal intercalated disc compared with wild-type mice

increased cardiomyocyte apoptosis ( J:170148 )

cellular

cardiac interstitial fibrosis ( J:170148 )

• at 10 months

increased cardiomyocyte apoptosis ( J:170148 )

Genotype
MGI:5906377

cn54

• Allelic Composition: Ptger4^tm1.1Matb/Ptger4^tm1.1Matb; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

cardiovascular system

abnormal cardiac muscle tissue morphology ( J:158439 )

♂ • myofiber disarray

abnormal myocardial fiber morphology ( J:158439 )

♂ • length of myocytes from 31-33 week old males is increased, whereas width is normal

increased heart weight ( J:158439 )

♂ • heart weight to body weight ratio is increased in aged males

cardiac hypertrophy ( J:158439 )

♂ • males develop eccentric hypertrophy

decreased heart left ventricle posterior wall thickness ( J:158439 )

♂ • males show reduced posterior wall thickness at diastole

dilated heart left ventricle ( J:158439 )

• dilated left ventricle in males and a slight increase in left ventricular dimension in females

cardiac interstitial fibrosis ( J:158439 )

♂ • 39% increase in interstitial collagen fraction and greater collagen deposition in hearts

dilated cardiomyopathy ( J:158439 )

• older males show reduced ejection fraction and dilated left ventricle, indicating development of dilated cardiomyopathy

• females develop dilated cardiomyopathy at an older age and to a lesser extent than males

decreased cardiac muscle contractility ( J:158439 )

• ejection fraction is lower in 23-33 week old males; two groups are evident, those mice with ejection fraction greater than 70% and those with ejection fraction less than 70%

• 30-32 week old females show a modest, but significant, decline in ejection fraction

• a decline in ejection fraction begins around 16 weeks of age in males and after 24-28 weeks of age in females

• however, systolic blood pressure is normal in males and females at 28 weeks of age

abnormal heart echocardiography feature ( J:158439 )

• 28 week old male mice at with ejection fraction less than 70% exhibit increased left ventricular mass, increased left ventricular dimension at systole and left ventricular dimension at diastole, and reduced posterior wall thickness at diastole

• 31 week old females exhibit increased left ventricular dimension at systole

heart inflammation ( J:158439 )

♂ • patches of infiltration cells in hearts, however, the percentage of macrophages is not different from wild-type mice

immune system

heart inflammation ( J:158439 )

♂ • patches of infiltration cells in hearts, however, the percentage of macrophages is not different from wild-type mice

muscle

abnormal cardiac muscle tissue morphology ( J:158439 )

♂ • myofiber disarray

abnormal myocardial fiber morphology ( J:158439 )

♂ • length of myocytes from 31-33 week old males is increased, whereas width is normal

dilated cardiomyopathy ( J:158439 )

• older males show reduced ejection fraction and dilated left ventricle, indicating development of dilated cardiomyopathy

• females develop dilated cardiomyopathy at an older age and to a lesser extent than males

decreased cardiac muscle contractility ( J:158439 )

• ejection fraction is lower in 23-33 week old males; two groups are evident, those mice with ejection fraction greater than 70% and those with ejection fraction less than 70%

• 30-32 week old females show a modest, but significant, decline in ejection fraction

• a decline in ejection fraction begins around 16 weeks of age in males and after 24-28 weeks of age in females

• however, systolic blood pressure is normal in males and females at 28 weeks of age

growth/size/body

increased heart weight ( J:158439 )

♂ • heart weight to body weight ratio is increased in aged males

cardiac hypertrophy ( J:158439 )

♂ • males develop eccentric hypertrophy

cellular

cardiac interstitial fibrosis ( J:158439 )

♂ • 39% increase in interstitial collagen fraction and greater collagen deposition in hearts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:158439

Genotype
MGI:3044594

cn55

• Allelic Composition: Edn1^tm1Ywa/Edn1^tm1Ywa; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

cardiovascular system

decreased response of heart to induced stress ( J:90390 , J:96386 )

• mice are resistant to hyperthyroid cardiac hypertrophy, showing a 57% reduction in cardiac hypertrophy in response to tri-iodothyronine (T3) relative to control mice (J:90390)

• left ventricular mass is increased by 3% in response to T3, compared to a 27% increase observed in similarly treated control mice (J:90390)

• the magnitude of Trypanosoma cruzi infection-associated cardiomyopathy is significantly less than in controls (J:96386)

homeostasis/metabolism

decreased response of heart to induced stress ( J:90390 , J:96386 )

• mice are resistant to hyperthyroid cardiac hypertrophy, showing a 57% reduction in cardiac hypertrophy in response to tri-iodothyronine (T3) relative to control mice (J:90390)

• left ventricular mass is increased by 3% in response to T3, compared to a 27% increase observed in similarly treated control mice (J:90390)

• the magnitude of Trypanosoma cruzi infection-associated cardiomyopathy is significantly less than in controls (J:96386)

Genotype
MGI:7344039

cn56

• Allelic Composition: Men1^tm1.2Ctre/Men1^tm1.2Ctre; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

normal phenotype

no abnormal phenotype detected ( J:127545 )

• mice are viable and fertile and exhibit no detectable heart defects

Genotype
MGI:5304713

cn57

• Allelic Composition: Egln1^tm1Kael/Egln1^tm1Kael; Egln3^tm1Vlcg/Egln3^tm1Vlcg; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

premature death ( J:179490 )

• mean survival is 29 weeks

cardiovascular system

increased angiogenesis ( J:179490 )

myocardial fiber degeneration ( J:179490 )

increased heart weight ( J:179490 )

• at 5 weeks and severe at 8 weeks

abnormal heart left ventricle morphology ( J:179490 )

• at 8 weeks, mice exhibit reduced left ventricular wall thickness and increased left ventricular end-diastolic dimension compared with control mice

decreased heart ventricle muscle contractility ( J:179490 )

• at 5 weeks and severe at 8 weeks

cardiomyopathy ( J:179490 )

• severe at 8 weeks of age

muscle

myocardial fiber degeneration ( J:179490 )

decreased heart ventricle muscle contractility ( J:179490 )

• at 5 weeks and severe at 8 weeks

cardiomyopathy ( J:179490 )

• severe at 8 weeks of age

cellular

decreased mitochondrial number ( J:179490 )

• myocytes exhibit mitochondrial loss

growth/size/body

increased heart weight ( J:179490 )

• at 5 weeks and severe at 8 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:179490

Genotype
MGI:5304715

cn58

• Allelic Composition: Egln1^tm1Kael/Egln1^tm1Kael; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

cardiovascular system

liver vascular congestion ( J:179490 )

• following thoracic aorta constriction, liver wet weight to dry weight is increased compared to in wild-type mice

pulmonary vascular congestion ( J:179490 )

• following thoracic aorta constriction, lung wet weight to dry weight is increased compared to in wild-type mice

increased angiogenesis ( J:179490 )

increased myocardial fiber size ( J:179490 )

• in aged mice

myocardial fiber degeneration ( J:179490 )

• following thoracic aorta constriction, mice exhibit myocyte dropout with replacement and interstitial fibrosis

enlarged heart ( J:179490 )

• following thoracic aorta constriction

increased heart weight ( J:179490 )

• following thoracic aorta constriction

abnormal heart left ventricle morphology ( J:179490 )

• following thoracic aorta constriction, mice exhibit increased left ventricular end-diastolic dimension compared with control mice

• aged mice exhibit left ventricular posterior wall thickness compared with control mice

cardiac interstitial fibrosis ( J:179490 )

• following thoracic aorta constriction

decreased heart ventricle muscle contractility ( J:179490 )

• following thoracic aorta constriction or left anterior descending artery and in aged mice

increased response of heart to induced stress ( J:179490 )

• following thoracic aorta constriction, mice exhibit increased cardiac hypertrophy, reduced cardiac function (decreased fractional shortening and increased left ventricular end-diastolic dimension and left ventricular posterior wall thickness), increased heart weight, cardiac interstitial fibrosis, enlarge myocardial fiber, and congestion in the lung and liver compared with wild-type mice

muscle

increased myocardial fiber size ( J:179490 )

• in aged mice

myocardial fiber degeneration ( J:179490 )

• following thoracic aorta constriction, mice exhibit myocyte dropout with replacement and interstitial fibrosis

decreased heart ventricle muscle contractility ( J:179490 )

• following thoracic aorta constriction or left anterior descending artery and in aged mice

homeostasis/metabolism

increased response of heart to induced stress ( J:179490 )

• following thoracic aorta constriction, mice exhibit increased cardiac hypertrophy, reduced cardiac function (decreased fractional shortening and increased left ventricular end-diastolic dimension and left ventricular posterior wall thickness), increased heart weight, cardiac interstitial fibrosis, enlarge myocardial fiber, and congestion in the lung and liver compared with wild-type mice

liver/biliary system

liver vascular congestion ( J:179490 )

• following thoracic aorta constriction, liver wet weight to dry weight is increased compared to in wild-type mice

respiratory system

pulmonary vascular congestion ( J:179490 )

• following thoracic aorta constriction, lung wet weight to dry weight is increased compared to in wild-type mice

cellular

cardiac interstitial fibrosis ( J:179490 )

• following thoracic aorta constriction

decreased mitochondrial number ( J:179490 )

• myocytes exhibit mitochondrial loss

growth/size/body

enlarged heart ( J:179490 )

• following thoracic aorta constriction

increased heart weight ( J:179490 )

• following thoracic aorta constriction

Genotype
MGI:5304716

cn59

• Allelic Composition: Gt(ROSA)26Sor^{tm4(HIF2A*)Kael}/Gt(ROSA)26Sor⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

liver/biliary system

liver vascular congestion ( J:179490 )

cardiovascular system

liver vascular congestion ( J:179490 )

pulmonary vascular congestion ( J:179490 )

increased angiogenesis ( J:179490 )

abnormal heart left ventricle morphology ( J:179490 )

• at 8 and 11 weeks, mice exhibit increased left ventricular end-diastolic dimension compared with control mice

cardiac fibrosis ( J:179490 )

• at 8 and 11 weeks

dilated cardiomyopathy ( J:179490 )

• 8 week old mice show signs of dilated cardiomyopathy including left ventricle dilatation and decreased fractional shortening

decreased heart ventricle muscle contractility ( J:179490 )

• at 8 and 11 weeks, mice exhibit reduced fractional shortening compared with control mice

respiratory system

pulmonary vascular congestion ( J:179490 )

muscle

dilated cardiomyopathy ( J:179490 )

• 8 week old mice show signs of dilated cardiomyopathy including left ventricle dilatation and decreased fractional shortening

decreased heart ventricle muscle contractility ( J:179490 )

• at 8 and 11 weeks, mice exhibit reduced fractional shortening compared with control mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:179490

Genotype
MGI:3046803

cn60

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm3Bld; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal aortic arch morphology ( J:91013 )

• at E18.5 only those aortic arch abnormalities present in Tbx1^tm1Bld heterozygotes are seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:91013

Genotype
MGI:3616709

cn61

• Allelic Composition: Mdm2^tm1Glo/Mdm2^tm2.1Glo; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:104114 )

• all die by E13.5, with abnormalities evident at E9.5 but not E9

growth/size/body

decreased embryo size ( J:104114 )

• smaller than controls, probably due to lack of blood flow, however they develop to the correct developmental stage

cardiovascular system

abnormal heart morphology ( J:104114 )

thin myocardium ( J:104114 )

• significant thinning of the myocardial layer in the ventricles

small heart ( J:104114 )

• heart mass is smaller in E9.5 embryos and by E13.5, most homozygotes lack any visible signs of a heart

abnormal heart ventricle morphology ( J:104114 )

• one of the E13.5 embryos that still has a heart shows abnormal trabeculation in the ventricle and abnormal ventricular wall structure

abnormal cardiovascular system physiology ( J:104114 )

• hearts fail to function properly as indicated by blood leaking outside the heart and the backup of blood in the atrium

abnormal blood circulation ( J:104114 )

• decrease in blood flow that results in congestion and backup of blood in other organs

hemorrhage ( J:104114 )

• exhibit blood leaking outside the heart

muscle

thin myocardium ( J:104114 )

• significant thinning of the myocardial layer in the ventricles

increased cardiomyocyte apoptosis ( J:104114 )

embryo

decreased embryo size ( J:104114 )

• smaller than controls, probably due to lack of blood flow, however they develop to the correct developmental stage

cellular

increased cardiomyocyte apoptosis ( J:104114 )

Genotype
MGI:4837486

cn62

• Allelic Composition: Rassf1^tm1.1Brd/Rassf1^tm1.1Brd; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB/N

cardiovascular system

decreased response of heart to induced stress ( J:165327 )

• following pressure overload hypertrophy, fibrosis and cardiomyocyte apoptosis are decreased and heart function is improved compared to wild-type controls

• in the absence of pressure overload, gross cardiac morphology is similar to controls

homeostasis/metabolism

decreased response of heart to induced stress ( J:165327 )

• following pressure overload hypertrophy, fibrosis and cardiomyocyte apoptosis are decreased and heart function is improved compared to wild-type controls

• in the absence of pressure overload, gross cardiac morphology is similar to controls

Genotype
MGI:5906349

cn63

• Allelic Composition: Dicer1^tm1Smr/Dicer1^tm1Smr; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB/N

Dilated cardiomyopathy in Dicer1^tm1Smr/Dicer1^tm1Smr Tg(Myh6-cre)2182Mds/0 hearts

growth/size/body

enlarged heart ( J:131962 )

mortality/aging

postnatal lethality, complete penetrance ( J:131962 )

• all mice die within 4 days after birth

behavior/neurological

decreased locomotor activity ( J:131962 )

• pups become fragile and exhibit decreased spontaneous activity preceding death

cardiovascular system

abnormal myocardial fiber morphology ( J:131962 )

• integrity of cardiomyocytes is impaired

disorganized myocardium ( J:131962 )

fetal cardiomyocyte disarray ( J:131962 )

• neonatal cardiomyocytes show disarrayed myofibrils

enlarged heart ( J:131962 )

dilated heart left ventricle ( J:131962 )

dilated cardiomyopathy ( J:131962 )

decreased heart ventricle muscle contractility ( J:131962 )

• decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

• hearts exhibit dysregulation of cardiac contractile protein expression

• however, sarcoplasmic reticulum calcium uptake rates are normal in hearts

abnormal heart echocardiography feature ( J:131962 )

• echocardiography indicates severe left ventricle dilation with a decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

decreased heart rate ( J:131962 )

• hearts only beat about half of the rate

congestive heart failure ( J:131962 )

cellular

increased cardiomyocyte apoptosis ( J:131962 )

• increase in apoptosis in the left atrium of P2 hearts and in restricted areas of the ventricular apex and left ventricle wall, however no increase in apoptosis is seen before P0

• however, cardiomyocyte proliferation, cell size, and cell number are normal

homeostasis/metabolism

abnormal atrial thrombosis ( J:131962 )

• accumulation of blood clots and/or thrombin in the left atrium

abnormal ventricular thrombosis ( J:131962 )

• accumulation of blood clots and/or thrombin in the left ventricle

muscle

abnormal myocardial fiber morphology ( J:131962 )

• integrity of cardiomyocytes is impaired

disorganized myocardium ( J:131962 )

dilated cardiomyopathy ( J:131962 )

decreased heart ventricle muscle contractility ( J:131962 )

• decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

• hearts exhibit dysregulation of cardiac contractile protein expression

• however, sarcoplasmic reticulum calcium uptake rates are normal in hearts

increased cardiomyocyte apoptosis ( J:131962 )

• increase in apoptosis in the left atrium of P2 hearts and in restricted areas of the ventricular apex and left ventricle wall, however no increase in apoptosis is seen before P0

• however, cardiomyocyte proliferation, cell size, and cell number are normal

abnormal sarcomere morphology ( J:131962 )

• less sarcomeres in heart ventricles and the sarcomeres that are present are disarrayed and shorter

• however, intercalated discs appear normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:131962

Genotype
MGI:5490257

cn64

• Allelic Composition: Fkbp1a^tm1.1Shou/Fkbp1a^tm1Zuk; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:195489 )

N • cardiac development appears normal

Genotype
MGI:3831703

cn65

• Allelic Composition: Hdac3^tm1.1Eno/Hdac3^tm1.1Eno; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S/SvEv * C57BL/6

growth/size/body

increased heart weight ( J:144604 )

• 72% increase in heart weight/body weight ratio by 12 weeks of age

cardiac hypertrophy ( J:144604 )

• signs of cardiac hypertrophy by 4 weeks of age

• hypertrophy exacerbated by 12 weeks of age

• both right and left atria are enlarged

• cardiomyocyte hypertrophy, particularly in the left ventricle free wall and the septum

mortality/aging

premature death ( J:144604 )

• significant lethality between 12 and 14 weeks of age

• 100% lethality by 16 weeks

cardiovascular system

cardiovascular system phenotype ( J:144604 )

N • normal sinus rhythm

increased cardiac muscle triglyceride level ( J:144604 )

• fasting myocardial triglycerides are increased after 24 hours

abnormal heart morphology ( J:144604 )

abnormal myocardial fiber mitochondrial morphology ( J:144604 )

• lack normal association with sarcomeres in cardiac muscle

abnormal heart size ( J:144604 )

increased heart weight ( J:144604 )

• 72% increase in heart weight/body weight ratio by 12 weeks of age

cardiac hypertrophy ( J:144604 )

• signs of cardiac hypertrophy by 4 weeks of age

• hypertrophy exacerbated by 12 weeks of age

• both right and left atria are enlarged

• cardiomyocyte hypertrophy, particularly in the left ventricle free wall and the septum

dilated heart left ventricle ( J:144604 )

• increased in both systole and diastole

cardiac interstitial fibrosis ( J:144604 )

decreased heart left ventricle muscle contractility ( J:144604 )

• reduced fractional shortening of the left ventricle

cellular

abnormal myocardial fiber mitochondrial morphology ( J:144604 )

• lack normal association with sarcomeres in cardiac muscle

cardiac interstitial fibrosis ( J:144604 )

abnormal mitochondrial crista morphology ( J:144604 )

• reduced density of cristae

abnormal cellular respiration ( J:144604 )

• 25% reduction in complex I activity

• 39% reduction in NADH oxidase activity

• two fold increase in free radical production

homeostasis/metabolism

abnormal lipid level ( J:144604 )

• accumulation of neutral lipids in ventricles but not atria

increased cardiac muscle triglyceride level ( J:144604 )

• fasting myocardial triglycerides are increased after 24 hours

muscle

increased cardiac muscle triglyceride level ( J:144604 )

• fasting myocardial triglycerides are increased after 24 hours

abnormal myocardial fiber mitochondrial morphology ( J:144604 )

• lack normal association with sarcomeres in cardiac muscle

decreased heart left ventricle muscle contractility ( J:144604 )

• reduced fractional shortening of the left ventricle

Genotype
MGI:3718388

cn66

• Allelic Composition: Hdac1^tm1.1Eno/Hdac1^tm1.1Eno; Hdac2^tm1.1Eno/Hdac2^tm1.1Eno; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CD-1 * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:123173 )

• mice die by day 14

cardiovascular system

dilated heart ventricle ( J:123173 )

• at P11, left and right ventricles are dilated

irregular heartbeat ( J:123173 )

• at P10, mice display cardiac arrhythmias

muscle

increased cardiomyocyte apoptosis ( J:123173 )

• mice have a three-fold increase in apoptosis compared to wild-type and control mice

cellular

increased cardiomyocyte apoptosis ( J:123173 )

• mice have a three-fold increase in apoptosis compared to wild-type and control mice

Genotype
MGI:3718385

cn67

• Allelic Composition: Hdac1^tm1.1Eno/Hdac1^tm1.1Eno; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CD-1 * FVB/N

normal phenotype

no abnormal phenotype detected ( J:123173 )

• mice are phenotypically normal and have no cardiac abnormalities

Genotype
MGI:3718387

cn68

• Allelic Composition: Hdac2^tm1.1Eno/Hdac2^tm1.1Eno; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CD-1 * FVB/N

normal phenotype

no abnormal phenotype detected ( J:123173 )

• mice are viable into adulthood and show no cardiac abnormalities

Genotype
MGI:3778390

cn69

• Allelic Composition: Prkd1^tm1Eno/Prkd1^tm1Eno; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S/SvEv * C57BL/6 * FVB/N

cardiovascular system

increased heart weight ( J:132803 )

• three weeks after surgical thoracic aortic constriction (TAC), mice have 50% less weight gain in the heart compared to wild-type mice

• mice only increase heart weight by 11% compared to 16% for wild-type mice after two weeks treatment with angiotensin II

• mice only increase heart weight by 21% compared to 37% increase in wild-type mice one week after isoproterenol treatment

abnormal heart left ventricle morphology ( J:132803 )

• three weeks after TAC surgery, mice have minimal increase in left ventricle wall thickness unlike wild-type mice that have pronounced thickening of the left ventricle wall in response to TAC

• mice are resistant to dilation of left ventricle that occurs three weeks after TAC surgery in wild-type mice

cardiac fibrosis ( J:132803 )

• mice have much less fibrosis of the heart three weeks after TAC surgery compared to wild-type mice

• less fibrosis also occurs compared to wild-type mice in response to angiotensin II treatment

increased cardiac muscle contractility ( J:132803 )

• mice do not display a decrease in fractional shortening three weeks after TAC surgery while wild-type mice have significant decreases

abnormal heart rate ( J:132803 )

• mice are resistant to reductions in heart rate that occur three weeks after thoracic aortic constriction (TAC) surgery

muscle

increased cardiac muscle contractility ( J:132803 )

• mice do not display a decrease in fractional shortening three weeks after TAC surgery while wild-type mice have significant decreases

growth/size/body

increased heart weight ( J:132803 )

• three weeks after surgical thoracic aortic constriction (TAC), mice have 50% less weight gain in the heart compared to wild-type mice

• mice only increase heart weight by 11% compared to 16% for wild-type mice after two weeks treatment with angiotensin II

• mice only increase heart weight by 21% compared to 37% increase in wild-type mice one week after isoproterenol treatment

Genotype
MGI:3713114

cn70

• Allelic Composition: Atg5^tm1Myok/Atg5^tm1Myok; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129S/SvEv * C57BL/6 * FVB/N

normal phenotype

no abnormal phenotype detected ( J:121778 )

• mice are normal

Genotype
MGI:5502749

cn71

• Allelic Composition: Atg5^tm1Myok/Atg5^tm1Myok; Rheb^tm1.1Otsu/Rheb^tm1.1Otsu; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S/SvEv * C57BL/6J * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:197831 )

• mice die around P10

Genotype
MGI:5544295

cn72

• Allelic Composition: Yap1^tm1.1Eno/Yap1^tm1.1Eno; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S/SvEv * FVB/N

Lethal cardiomyopathy in Yap1^tm1.1Eno/Yap1^tm1.1Eno Tg(Myh6-cre)2182Mds/0 mice

mortality/aging

premature death ( J:200670 )

• die between 11 and 20 weeks of age from heart failure

cardiovascular system

thin ventricular wall ( J:200670 )

• develops by 9 weeks of age

dilated heart ventricle ( J:200670 )

• mild dilation is seen at 6 weeks of age and becomes more pronounced at 12 weeks of age

cardiac fibrosis ( J:200670 )

• develops in older mice with dilated cardiomyopathy

abnormal cardiovascular system physiology ( J:200670 )

• mild functional heart deficits by 6 weeks of age

dilated cardiomyopathy ( J:200670 )

• develops by 9 weeks of age and worsens with age

decreased cardiac muscle contractility ( J:200670 )

• mild at 6 weeks of age and becomes more pronounced at 12 weeks of age

increased myocardial infarct size ( J:200670 )

• at 26 days after permanent ligation of the left anterior descending coronary artery at P2, mice display a gross deficiency of healthy myocardial tissue throughout the LV free wall and extensive fibrotic infarct zone unlike controls that have fully regenerated by this time

behavior/neurological

lethargy ( J:200670 )

• become lethargic between 11 and 20 weeks of age

respiratory system

respiratory distress ( J:200670 )

• develops between 11 and 20 weeks of age

homeostasis/metabolism

increased myocardial infarct size ( J:200670 )

• at 26 days after permanent ligation of the left anterior descending coronary artery at P2, mice display a gross deficiency of healthy myocardial tissue throughout the LV free wall and extensive fibrotic infarct zone unlike controls that have fully regenerated by this time

abnormal atrial thrombosis ( J:200670 )

• develops in older mice with dilated cardiomyopathy

muscle

dilated cardiomyopathy ( J:200670 )

• develops by 9 weeks of age and worsens with age

decreased cardiac muscle contractility ( J:200670 )

• mild at 6 weeks of age and becomes more pronounced at 12 weeks of age

Genotype
MGI:5544299

cn73

• Allelic Composition: Wwtr1^tm1.1Eno/Wwtr1^tm1.1Eno; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S/SvEv * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:200670 )

N • no obvious cardiac defects

Genotype
MGI:5544298

cn74

• Allelic Composition: Wwtr1^tm1.1Eno/Wwtr1^tm1.1Eno; Yap1^tm1.1Eno/Yap1^tm1.1Eno; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S/SvEv * FVB/N

Wwtr1^tm1.1Eno/Wwtr1^tm1.1Eno Yap1^tm1.1Eno/Yap1^tm1.1Eno Tg(Myh6-cre)2182Mds/0 mice exhibit cardiac abnormalities and Wwtr1^tm1.1Eno/Wwtr1⁺ Yap1^tm1.1Eno/Yap1^tm1.1Eno Tg(Myh6-cre)2182Mds/0 hearts show defects in proliferation and survival

mortality/aging

neonatal lethality, complete penetrance ( J:200670 )

• all die by P1

cardiovascular system

abnormal heart morphology ( J:200670 )

• severe cardiac defects

Genotype
MGI:5544296

cn75

• Allelic Composition: Wwtr1^tm1.1Eno/Wwtr1^tm1.1Eno; Yap1^tm1.1Eno/Yap1⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S/SvEv * FVB/N

Cardiomyopathy in Wwtr1^tm1.2Eno/Wwtr1^tm1.2Eno Yap1^tm1.1Eno/Yap1⁺ Tg(Myh6-cre)2182Mds/0 mice

mortality/aging

premature death ( J:200670 )

• complete lethality by 33 weeks of age from heart failure

cardiovascular system

dilated cardiomyopathy ( J:200670 )

• grossly dilated at 30 weeks of age but seen as early as 8 days of age

homeostasis/metabolism

abnormal atrial thrombosis ( J:200670 )

• at 30 weeks of age

muscle

dilated cardiomyopathy ( J:200670 )

• grossly dilated at 30 weeks of age but seen as early as 8 days of age

Genotype
MGI:5544297

cn76

• Allelic Composition: Wwtr1^tm1.1Eno/Wwtr1⁺; Yap1^tm1.1Eno/Yap1^tm1.1Eno; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S/SvEv * FVB/N

Cardiomyopathy in Wwtr1^tm1.2Eno/Wwtr1⁺ Yap1^tm1.1Eno/Yap1^tm1.1Eno Tg(Myh6-cre)2182Mds/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:200670 )

• die by 10 days of age

• lethality is accelerated compared to mutant mice wild type for Wwtr1

cardiovascular system

myocardium hypoplasia ( J:200670 )

• about a 60% decrease in the number of cardiomyocytes

thin myocardium ( J:200670 )

cellular

increased cardiomyocyte apoptosis ( J:200670 )

• in neonates

muscle

myocardium hypoplasia ( J:200670 )

• about a 60% decrease in the number of cardiomyocytes

thin myocardium ( J:200670 )

increased cardiomyocyte apoptosis ( J:200670 )

• in neonates

Genotype
MGI:5491820

cn77

• Allelic Composition: Rock2^tm2Liao/Rock2^tm2Liao; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: 129/Sv * C57BL/6

cardiovascular system

cardiovascular system phenotype ( J:196433 )

N • no anatomical or functional cardiac abnormalities before 25 weeks of age

N • increase in systolic blood pressure in response to Ang II is similar to controls

abnormal heart morphology ( J:196433 )

• less fibrosis than controls from Ang II infusion

abnormal heart size ( J:196433 )

• less cardiac hypertrophy than controls from Ang II infusion

• less cardiac hypertrophy due to trans aortic constriction

Genotype
MGI:5907041

cn78

• Allelic Composition: Myocd^tm1Msp/Myocd^tm1Msp; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129/Sv * FVB/N

mortality/aging

premature death ( J:154666 )

• 90% of mice die by 10 months of age and no mice survive beyond 1 year of age

postnatal lethality, incomplete penetrance ( J:154666 )

• about 20% of mice die before 3 weeks of age

cardiovascular system

abnormal myocardial fiber morphology ( J:154666 )

• extensive loss of myofibrillar striations

abnormal intercalated disk morphology ( J:154666 )

• intercalated discs of hearts appear abnormal

• serpiginous intercalated discs with indistinct desmosomes and adherens junctions

myocardial fiber degeneration ( J:154666 )

• hearts show extensive loss of cardiomyocytes

increased heart atrium size ( J:154666 )

• both the left and right atrium are enlarged in 10 month old mice

enlarged heart ( J:154666 )

• four-chamber enlargement in 10 month old mice

increased heart ventricle size ( J:154666 )

• both the left and right ventricles are enlarged in 10 month old mice

pericardial effusion ( J:154666 )

cardiac fibrosis ( J:154666 )

• 11.2% of the left ventricle myocardium shows fibrosis compared to 0.46% in controls

dilated cardiomyopathy ( J:154666 )

• mice develop lethal dilated cardiomyopathy

decreased cardiac muscle contractility ( J:154666 )

• systolic function is depressed

• mean ejection fraction is reduced (24.5% vs 57.8% in controls)

abnormal heart echocardiography feature ( J:154666 )

• echocardiography shows enlargement of the left atrium, left ventricle, right atrium, and right ventricle in 10 month old hearts

homeostasis/metabolism

pericardial effusion ( J:154666 )

abnormal cardiac thrombosis ( J:154666 )

• atrial and ventricular thromboses are seen in 10 month old hearts

abnormal atrial thrombosis ( J:154666 )

• atrial thromboses are seen in 10 month old hearts

muscle

abnormal myocardial fiber morphology ( J:154666 )

• extensive loss of myofibrillar striations

abnormal intercalated disk morphology ( J:154666 )

• intercalated discs of hearts appear abnormal

• serpiginous intercalated discs with indistinct desmosomes and adherens junctions

myocardial fiber degeneration ( J:154666 )

• hearts show extensive loss of cardiomyocytes

dilated cardiomyopathy ( J:154666 )

• mice develop lethal dilated cardiomyopathy

decreased cardiac muscle contractility ( J:154666 )

• systolic function is depressed

• mean ejection fraction is reduced (24.5% vs 57.8% in controls)

abnormal sarcomere morphology ( J:154666 )

• shortened, hypercontracted sarcomeres in hearts

growth/size/body

enlarged heart ( J:154666 )

• four-chamber enlargement in 10 month old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:154666

Genotype
MGI:3802663

cn79

• Allelic Composition: Ppargc1a^tm1Dpk/Ppargc1a^tm1Dpk; Ppargc1b^tm1Dpk/Ppargc1b^tm1Dpk; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129X1/SvJ * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:137598 )

• all mice die by day 7

neonatal lethality, incomplete penetrance ( J:137598 )

• 67% of mice die within 24 hours of birth

cardiovascular system

abnormal myocardium layer morphology ( J:137598 )

• after birth, myocytes exhibit a reduction in mitochondrial number and size compared to in wild-type mice

decreased cardiac output ( J:137598 )

• similar to that found in Ppargc1a^tm1Dpk Ppargc1b^tm1.1Dpk homozygotes

muscle

abnormal myocardium layer morphology ( J:137598 )

• after birth, myocytes exhibit a reduction in mitochondrial number and size compared to in wild-type mice

Genotype
MGI:7444863

cn80

• Allelic Composition: Lemd2^em2Eno/Lemd2^em2Eno; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6N * FVB/N

mortality/aging

neonatal lethality, incomplete penetrance ( J:331716 )

• mice show neonatal lethality, with 50% mortality by 2 days of age

growth/size/body

decreased body size ( J:331716 )

• mice show a reduction in body size immediately after birth

cardiovascular system

abnormal heart morphology ( J:331716 )

• cardiac sections from 5-day-old hearts show 6% of the total nuclei being positive for H2AX phosphorylation, indicating an increase in DNA damage

abnormal myocardial fiber morphology ( J:331716 )

• cardiomyocytes from P1 hearts exhibit bigger nuclei than controls at both baseline and after compression (subjected to mechanical stress), indicating nuclear instability and alterations in chromatin organization

dilated heart atrium ( J:331716 )

dilated heart ventricle ( J:331716 )

abnormal cardiovascular system physiology ( J:331716 )

• cardiac sections from 5-day-old hearts show a decrease in cellular proliferation and an increase in apoptotic cells

• the percentage of apoptotic nuclei is almost the same as the percentage of cells that show DNA damage, suggesting that DNA damage triggers cell death

dilated cardiomyopathy ( J:331716 )

• dilation of atrial and ventricular chambers

abnormal heart echocardiography feature ( J:331716 )

• echocardiography shows a reduction in both ejection fraction and fractional shortening within the first 10 days of life

• mice show systolic dysfunction with severely impaired contraction of the left ventricle

abnormal myocardial fiber physiology ( J:331716 )

• cardiomyocytes isolated from P1 hearts subjected to mechanical stretching triggers exacerbated DNA damage

• cardiomyocytes fail to adapt to mechanical stress and nuclei show blebs rather than increasing their solidity indicating that nuclear envelope is more susceptible to deformations under mechanical stress

muscle

abnormal myocardial fiber morphology ( J:331716 )

• cardiomyocytes from P1 hearts exhibit bigger nuclei than controls at both baseline and after compression (subjected to mechanical stress), indicating nuclear instability and alterations in chromatin organization

dilated cardiomyopathy ( J:331716 )

• dilation of atrial and ventricular chambers

Genotype
MGI:4421539

cn81

• Allelic Composition: Abl1^tm1Goff/Abl1^tm1Goff; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:156743 )

• most die shortly after birth

cardiovascular system

cardiovascular system phenotype ( J:156743 )

N • compared to homozygous mutant mice not carrying the cre transgene, cardiomyocyte overproliferation and ventricular lumen size reduction are dramatically reduced

thick ventricular wall ( J:156743 )

• not as thick as in homozygous mutant mice not carrying the cre transgene but slightly thicker than in heterozygous controls

Genotype
MGI:3045423

cn82

• Allelic Composition: Lpl^tm1Ijg/Lpl^tm1Ijg; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: C57BL/6

homeostasis/metabolism

abnormal glucose homeostasis ( J:90737 )

• basal glucose uptake by the heart increased 8 fold

• tendency for insulin stimulated glucose uptake by the heart to increase somewhat

abnormal lipid level ( J:90737 )

• heart uptake of VLDL decreased by 72%

decreased cardiac muscle triglyceride level ( J:90737 )

• heart content of triglycerides is decreased

increased circulating triglyceride level ( J:90737 )

• plasma triglyceride levels significantly elevated in males because of increased VLDL triglycerides

• plasma triglyceride levels in females also tended to be elevated but not significantly

• postprandial levels tended to remain elevated

increased circulating VLDL triglyceride level ( J:90737 )

decreased fatty acids level ( J:90737 )

• heart content of fatty acids is decreased

cardiovascular system

decreased cardiac muscle triglyceride level ( J:90737 )

• heart content of triglycerides is decreased

increased cardiac muscle cell glucose uptake ( J:90737 )

• basal glucose uptake by the heart increased 8-fold

• tendency for insulin stimulated glucose uptake by the heart to increase somewhat

muscle

decreased cardiac muscle triglyceride level ( J:90737 )

• heart content of triglycerides is decreased

increased cardiac muscle cell glucose uptake ( J:90737 )

• basal glucose uptake by the heart increased 8-fold

• tendency for insulin stimulated glucose uptake by the heart to increase somewhat

cellular

increased cardiac muscle cell glucose uptake ( J:90737 )

• basal glucose uptake by the heart increased 8-fold

• tendency for insulin stimulated glucose uptake by the heart to increase somewhat

Genotype
MGI:3032514

cn83

• Allelic Composition: Rce1^tm2Kim/Rce1^tm2.1Kim; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6

mortality/aging

premature death ( J:87958 )

• some mice died 3 to 5 months after birth

• 50% had died by 7 months of age

• 70% had died by 10 months of age

behavior/neurological

lethargy ( J:87958 )

• mice were listless several weeks prior to death

cardiovascular system

thin myocardium ( J:87958 )

• thin and dystrophic left ventricular musculature

• increased collagen between ventricular myoctes

enlarged heart ( J:87958 )

• histological analysis revealed dilation of all four chambers

dilated heart left ventricle ( J:87958 )

dilated heart right ventricle ( J:87958 )

dilated cardiomyopathy ( J:87958 )

homeostasis/metabolism

abnormal atrial thrombosis ( J:87958 )

• organized thrombi occasionally noted in left atria

edema ( J:87958 )

• pleural and peritoneal fluid accumulation observed upon autopsy

muscle

thin myocardium ( J:87958 )

• thin and dystrophic left ventricular musculature

• increased collagen between ventricular myoctes

dilated cardiomyopathy ( J:87958 )

integument

disheveled coat ( J:87958 )

• observed several weeks prior to death

growth/size/body

enlarged heart ( J:87958 )

• histological analysis revealed dilation of all four chambers

Genotype
MGI:7718681

cn84

• Allelic Composition: Nsun3^tm1.1Tomik/Nsun3^tm1.1Tomik; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * FVB/N

growth/size/body

enlarged heart ( J:336777 )

• older mice show mild heart enlargement, most likely due to compensatory response to compromised heart function

increased heart weight ( J:336777 )

• hearts exhibit normal weight in young mice (14-weeks-old) but are 31% heavier than controls in old mice (50-weeks old)

• however, body weight is normal at 13-20 weeks of age

cardiovascular system

abnormal myocardial fiber mitochondrial morphology ( J:336777 )

• heart mitochondria exhibit fragmented cristae

• mean size of heart mitochondria is 1.5 times larger than in controls at 14 weeks of age and 1.7 times larger at 50 weeks of age

• 50-week-old heart mitochondria are 17% larger than 14-week-old mitochondria

enlarged heart ( J:336777 )

• older mice show mild heart enlargement, most likely due to compensatory response to compromised heart function

increased heart weight ( J:336777 )

• hearts exhibit normal weight in young mice (14-weeks-old) but are 31% heavier than controls in old mice (50-weeks old)

• however, body weight is normal at 13-20 weeks of age

abnormal cardiovascular system physiology ( J:336777 )

• hearts show a mild increase in lactate levels, which may indicate that glycolysis activity is enhanced

increased cardiac muscle contractility ( J:336777 )

abnormal heart echocardiography feature ( J:336777 )

• echocardiography shows that relative mass of the left ventricle tends (not significantly) to be larger in older mice, but is normal in young mice, left ventricle volume is decreased in the systolic phase of hearts at 14 weeks of age, ejection fraction tends to be increased (not significantly), and the left ventricle thickness is increased in the systolic phase of 50-week-old heart, indicating enhanced heart contraction

cellular

abnormal myocardial fiber mitochondrial morphology ( J:336777 )

• heart mitochondria exhibit fragmented cristae

• mean size of heart mitochondria is 1.5 times larger than in controls at 14 weeks of age and 1.7 times larger at 50 weeks of age

• 50-week-old heart mitochondria are 17% larger than 14-week-old mitochondria

abnormal mitochondrial physiology ( J:336777 )

• heart mitochondria show a decrease of complex IV at 14 and 50 weeks of age and a decrease in the steady-state level of MT-CO1 protein, a mtDNA-encoded complex IV protein

• 14-week-old heart mitochondria show a decrease in complex IV activity and 50-week-old heart mitochondria show an additional decrease in complex I activity compared to 14-week old hearts

• however, the steady-state levels of mt-mRNAs are not affected

muscle

abnormal myocardial fiber mitochondrial morphology ( J:336777 )

• heart mitochondria exhibit fragmented cristae

• mean size of heart mitochondria is 1.5 times larger than in controls at 14 weeks of age and 1.7 times larger at 50 weeks of age

• 50-week-old heart mitochondria are 17% larger than 14-week-old mitochondria

increased cardiac muscle contractility ( J:336777 )

Genotype
MGI:5805256

cn85

• Allelic Composition: Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB/N

mortality/aging

premature death ( J:229455 )

• median lifespan of 46 weeks

cardiovascular system

cardiac muscle necrosis ( J:229455 )

• ongoing cardiomyocyte necrotic cell death

abnormal heart morphology ( J:229455 )

• hearts show increased endogenous glucose levels and decreased lactate levels

• however, levels of citric acid cycle intermediates are not altered

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

dilated heart left ventricle ( J:229455 )

• dilated left ventricular chamber

• however, left ventricular mass is preserved

cardiac fibrosis ( J:229455 )

• myocardial fibrosis

abnormal cardiovascular system physiology ( J:229455 )

• progressive heart dysfunction which becomes apparent at 20 weeks

• mice fed a high-fat diet beginning at 9 weeks of age show normal cardiac glucose uptake, normal levels of endogenous cardiac glucose and acylcarnitine, restoration of cardiac function, prevention of cardiac fibrosis, normal exercise tolerance and left ventricular ejection fraction, suppressed heart failure and restored life span

dilated cardiomyopathy ( J:229455 )

• dilated cardiomyopathy progresses to heart failure in middle age

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased heart left ventricle muscle contractility ( J:229455 )

• reduction in percentage of left ventricular ejection fraction

congestive heart failure ( J:229455 )

growth/size/body

weight loss ( J:229455 )

• weight loss before death

homeostasis/metabolism

increased circulating troponin T level ( J:229455 )

• increase in serum cardiac troponin T levels

cellular

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased mitochondrial size ( J:229455 )

• smaller mitochondria with normal cristae architecture in hearts

abnormal mitochondrial physiology ( J:229455 )

• specific activities of mitochondrial complexes II, III, and IV are increased in cardiomyocytes

• only moderately impaired ATP synthesis by complex V in hearts

muscle

abnormal myocardial fiber mitochondrial morphology ( J:229455 )

• distorted mitochondrial morphology in cardiomyocytes

• mice fed a high-fat diet beginning at 9 weeks of age still contain distorted mitochondria

cardiac muscle necrosis ( J:229455 )

• ongoing cardiomyocyte necrotic cell death

abnormal muscle physiology ( J:229455 )

• in vitro cardiomyocyte glycolysis rates are increased

• global reduction of total cardiac acylcarnitines, indicating reduced beta oxidation in cardiomyocytes

dilated cardiomyopathy ( J:229455 )

• dilated cardiomyopathy progresses to heart failure in middle age

increased cardiac muscle cell glucose uptake ( J:229455 )

• cardiac glucose uptake is increased

decreased heart left ventricle muscle contractility ( J:229455 )

• reduction in percentage of left ventricular ejection fraction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:229455

Genotype
MGI:5805258

cn86

• Allelic Composition: Oma1^tm1Tlan/Oma1^tm1Tlan; Yme1l1^tm1Tlan/Yme1l1^tm1Tlan; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrl * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:229455 )

N • mice exhibit normal cardiac function and mitochondrial morphology in hearts, and do not exhibit myocardial fibrosis

Genotype
MGI:7546788

cn87

• Allelic Composition: Creld1^{tm1c(EUCOMM)Wtsi}/Creld1^{tm1c(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * FVB/N * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:304446 )

• a few homozygotes survive to P13; no viable homozygotes are recovered at weaning age

neonatal lethality, incomplete penetrance ( J:304446 )

• although viable homozygous embryos are present at Mendelian ratios at E10.5 and E13.5, most homozygotes die shortly after birth due to heart failure

growth/size/body

decreased body size ( J:304446 )

decreased body weight ( J:304446 )

• at P0-P13, body weight is significantly lower than in control littermates

cardiovascular system

abnormal trabecula carnea morphology ( J:304446 )

• at E13.5, trabeculae are morphologically distinct and not yet compacting

• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae

ventricle myocardium hypoplasia ( J:304446 )

• at P0, P5 and P7, ventricles show myocardial hypoplasia

abnormal heart development ( J:304446 )

• transcriptome analysis shows altered transcriptional networks in both atria and ventricles at P3

• at E13.5, hearts show extracellular matrix (ECM) remodeling, as indicated by increased expression of Fn1 (fibronectin 1) and Lamb3 (laminin, beta 3)

• at E13.5, surface expression of Jag1 (jagged 1) on myocardial (Vcam1+) cells is reduced, leading to altered Notch1 signaling and heart development

• however, no defects in proliferation are noted in the atria or ventricles and no increased cell death is detected at E13.5

increased heart atrium size ( J:304446 )

• at P0, P5 and P7, atria are severely enlarged

cardiac fibrosis ( J:304446 )

• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae

• the fibrotic area is significantly increased in both the atria and ventricles relative to control mice

cardiovascular shunt ( J:304446 )

• at E13.5, mice exhibit an intraventricular shunt (IVS), whereas ventricles are already fully septated in control embryos

congestive heart failure ( J:304446 )

• homozygotes die shortly after birth due to heart failure

cellular

abnormal extracellular matrix morphology ( J:304446 )

• at E13.5, hearts show extracellular matrix (ECM) accumulation, as indicated by increased expression of Fn1 (fibronectin 1) and Lamb3 (laminin, beta 3)

muscle

abnormal trabecula carnea morphology ( J:304446 )

• at E13.5, trabeculae are morphologically distinct and not yet compacting

• at P0, P5 and P7, hearts exhibit collagen accumulation around the ventricular trabeculae

ventricle myocardium hypoplasia ( J:304446 )

• at P0, P5 and P7, ventricles show myocardial hypoplasia

Genotype
MGI:4830886

cn88

• Allelic Composition: Nox4^tm1.1Jusa/Nox4^tm1.1Jusa; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * FVB

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:163751 )

• reduced mortality in response to applied transverse aortic constriction induced pressure overload

cellular

cardiac interstitial fibrosis ( J:163751 )

• in response to pressure overload exhibit significantly attenuated interstitial fibrosis

decreased cardiomyocyte apoptosis ( J:163751 )

• in response to pressure overload exhibit significantly decreased TUNEL positive cells compared to wild-type

abnormal mitochondrial physiology ( J:163751 )

• superoxide production, in the mitochondria in response to transverse aortic constriction induced pressure overload is abolished compared to wild-type

• mitochondrial swelling, cytochrome c release, and a decrease in both mitochondrial DNA and aconitase activity in response to pressure overload are attenuated compared to wild-type

oxidative stress ( J:163751 )

• decreased production of superoxide in left ventricular myocardial sections

cardiovascular system

heart left ventricle hypertrophy ( J:163751 )

• in response to pressure overload exhibit significantly attenuated cardiac hypertrophy

cardiac interstitial fibrosis ( J:163751 )

• in response to pressure overload exhibit significantly attenuated interstitial fibrosis

decreased heart ventricle muscle contractility ( J:163751 )

• decrease in echocardiographically evaluated LV ejection fraction (EF) and fractional shortening in response to transverse aortic constriction induced pressure overload

decreased heart left ventricle muscle contractility ( J:163751 )

• decrease in echocardiographically evaluated LV ejection fraction (EF) and fractional shortening in response to transverse aortic constriction induced pressure overload

decreased response of heart to induced stress ( J:163751 )

• better cardiac function compared to wild-type in response to transverse aortic constriction induced pressure overload

muscle

heart left ventricle hypertrophy ( J:163751 )

• in response to pressure overload exhibit significantly attenuated cardiac hypertrophy

decreased heart ventricle muscle contractility ( J:163751 )

• decrease in echocardiographically evaluated LV ejection fraction (EF) and fractional shortening in response to transverse aortic constriction induced pressure overload

decreased heart left ventricle muscle contractility ( J:163751 )

• decrease in echocardiographically evaluated LV ejection fraction (EF) and fractional shortening in response to transverse aortic constriction induced pressure overload

decreased cardiomyocyte apoptosis ( J:163751 )

• in response to pressure overload exhibit significantly decreased TUNEL positive cells compared to wild-type

homeostasis/metabolism

decreased response of heart to induced stress ( J:163751 )

• better cardiac function compared to wild-type in response to transverse aortic constriction induced pressure overload

growth/size/body

heart left ventricle hypertrophy ( J:163751 )

• in response to pressure overload exhibit significantly attenuated cardiac hypertrophy

Genotype
MGI:6857772

cn89

• Allelic Composition: Fdps^tm1Jiy/Fdps^tm1Jiy; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

premature death ( J:317808 )

• mice show poor overall survival, with most mice dying within 4 months after birth

cardiovascular system

increased myocardial fiber size ( J:317808 )

• cross-sectional area of cardiomyocytes is increased at 2 months of age

enlarged heart ( J:317808 )

• hearts show enlargement beginning at 2 months of age

• mice show age-specific increases in chamber volume

increased heart weight ( J:317808 )

• mice exhibit a greater heart weight and heart weight to body weight ratio at 2 months of age

• mice treated with a farnesyltransferase inhibitor FTI-277 exhibit reduced heart weight/body weight ratio

cardiac hypertrophy ( J:317808 )

• expression of hypertrophic makers begins to increase at 1 month of age indicating cardiac hypertrophy

cardiac interstitial fibrosis ( J:317808 )

• diffuse interstitial fibrosis is seen in hearts from 3 months onward

increased cardiac stroke volume ( J:317808 )

• stroke volume gradually increases

decreased cardiac muscle contractility ( J:317808 )

• fractional shortening and ejection fraction begin to decline at 2 months of age

• mice treated with a farnesyltransferase inhibitor FTI-277 exhibit improved cardiac function

abnormal heart echocardiography feature ( J:317808 )

• transthoracic echocardiography shows that ejection fraction and fractional shortening begin to decline at 2 months of age and end diastolic volume (EDV), end systolic volume (ESV), left ventricular internal dimension in diastole (LVIDd), left ventricular internal dimension in systole (LVIDs) and stroke volume gradually increase

• however, no difference in left ventricular posterior wall thickness in diastole (LVPWd) is seen

growth/size/body

enlarged heart ( J:317808 )

• hearts show enlargement beginning at 2 months of age

• mice show age-specific increases in chamber volume

increased heart weight ( J:317808 )

• mice exhibit a greater heart weight and heart weight to body weight ratio at 2 months of age

• mice treated with a farnesyltransferase inhibitor FTI-277 exhibit reduced heart weight/body weight ratio

cardiac hypertrophy ( J:317808 )

• expression of hypertrophic makers begins to increase at 1 month of age indicating cardiac hypertrophy

homeostasis/metabolism

abnormal autophagy ( J:317808 )

• LC3b (Map1lc3b) levels are higher in mice and levels do not change after bafilomycin-A1 administration, indicating that autophagy flux is reduced

muscle

increased myocardial fiber size ( J:317808 )

• cross-sectional area of cardiomyocytes is increased at 2 months of age

decreased cardiac muscle contractility ( J:317808 )

• fractional shortening and ejection fraction begin to decline at 2 months of age

• mice treated with a farnesyltransferase inhibitor FTI-277 exhibit improved cardiac function

cellular

cardiac interstitial fibrosis ( J:317808 )

• diffuse interstitial fibrosis is seen in hearts from 3 months onward

abnormal autophagy ( J:317808 )

• LC3b (Map1lc3b) levels are higher in mice and levels do not change after bafilomycin-A1 administration, indicating that autophagy flux is reduced

Genotype
MGI:5566535

cn90

• Allelic Composition: Rbm20^tm2.1Hgra/Rbm20⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * FVB/N

cardiovascular system

abnormal myocardial fiber morphology ( J:208676 )

• reduced stiffness under passive stress

abnormal heart left ventricle morphology ( J:208676 )

• prolonged deceleration time of the E wave suggests a reduced diastolic left ventricular chamber stiffness

homeostasis/metabolism

abnormal exercise endurance ( J:208676 )

• increased maximal running speed on a free-running wheel

• however, mean running distance is normal

muscle

abnormal myocardial fiber morphology ( J:208676 )

• reduced stiffness under passive stress

Genotype
MGI:4421818

cn91

• Allelic Composition: Klf5^tm2.1Rng/Klf5^tm2.1Rng; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * FVB/N

Cardiomyocyte-specific deletion of Klf5 does not alter pressure overload-induced hypertrophy in Klf5^tm2.1Rng/Klf5^tm2.1Rng Tg(Myh6-cre)2182Mds/0 mice

cardiovascular system

cardiovascular system phenotype ( J:156696 )

N • mice exhibit a normal response to low-intensity transverse aortic constriction

Genotype
MGI:4836055

cn92

• Allelic Composition: Atp6ap2^tm1.1Aich/Y; Tg(Myh6-cre)2182Mds/?
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:165020 )

♂ • die within 3 weeks of birth

♂ • born at expected ratios

cardiovascular system

abnormal heart morphology ( J:165020 )

♂ • clusters of degenerating cardiomyocytes with extensive vacuolation in areas of replacement fibrosis

♂ • myofibrils and mitochondria exclusively at the cell periphery of cardiomyocytes

♂ • no gross cardiac anomalies at birth

abnormal heart weight ( J:165020 )

♂ • heart body ratio is significantly increased starting at day 14

abnormal cardiovascular system physiology ( J:165020 )

♂ • ventricular function severely impaired at 18 days of age

decreased heart ventricle muscle contractility ( J:165020 )

♂ • fractional shortening in ventricles is 12.9% compared to 27.7% for controls at 18 days of age

muscle

decreased heart ventricle muscle contractility ( J:165020 )

♂ • fractional shortening in ventricles is 12.9% compared to 27.7% for controls at 18 days of age

Genotype
MGI:5526029

cn93

• Allelic Composition: Nr3c1^tm1.1Jaci/Nr3c1^tm1.1Jaci; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

premature death ( J:201995 )

• increase morbidity and mortality by 5 months

• 7 months median survival age

• male mice have a median survival age of 8 months while this is only 6 months for female mice

respiratory system

abnormal lung morphology ( J:201995 )

♂ • free erythrocytes in alveoli and hemosiderin-laden macrophages (heart failure cells) within alveolar spaces (at 6 months of age

respiratory distress ( J:201995 )

growth/size/body

enlarged heart ( J:201995 )

♂ • in nearly all mice examined

increased heart weight ( J:201995 )

♂ • at 3 months of age

cardiac hypertrophy ( J:201995 )

♂

abnormal thoracic cavity morphology ( J:201995 )

♂ • in the majority of mice examined

immune system

heart inflammation ( J:201995 )

♂ • indicated by expression analysis

homeostasis/metabolism

abnormal atrial thrombosis ( J:201995 )

♂ • characterized by lamellation of fibrin and inflammatory cells, chronic inflammation, fibrosis, and neovascularization

abnormal calcium ion homeostasis ( J:201995 )

♂ • isolated cardiomyocytes fail to show a sustained increase in intracellular calcium following exposure to low concentrations of caffeine

muscle

increased myocardial fiber size ( J:201995 )

♂ • about a 140% increase in cardiomyocyte cross-sectional area at 3 months of age

♂ • adrenalectomy at 2 months of age does not reduce the increase in cardiomyocyte size seen at 6 months of age

decreased heart left ventricle muscle contractility ( J:201995 )

♂ • variable decrease in ejection fraction and increase in the left ventricular end-systolic dimension at 3 months of age

cardiovascular system

cardiovascular system phenotype ( J:201995 )

♂N • despite cardiac remodeling and reduced heart function, no electrocardiogram abnormalities are detected in mice at 3 - 6 months of age

increased myocardial fiber size ( J:201995 )

♂ • about a 140% increase in cardiomyocyte cross-sectional area at 3 months of age

♂ • adrenalectomy at 2 months of age does not reduce the increase in cardiomyocyte size seen at 6 months of age

enlarged heart ( J:201995 )

♂ • in nearly all mice examined

increased heart weight ( J:201995 )

♂ • at 3 months of age

cardiac hypertrophy ( J:201995 )

♂

increased heart left ventricle weight ( J:201995 )

♂ • at 3 months of age

dilated heart left ventricle ( J:201995 )

♂ • marked

thick ventricular wall ( J:201995 )

♂ • at 3 months

cardiac fibrosis ( J:201995 )

♂ • associated with atrial thrombosis

♂ • NORMAL: not detected in the ventricular wall at 3 months of age

poor circulation ( J:201995 )

♂ • atrial thrombosis is consistent with atrial blood stasis

decreased heart left ventricle muscle contractility ( J:201995 )

♂ • variable decrease in ejection fraction and increase in the left ventricular end-systolic dimension at 3 months of age

abnormal heart echocardiography feature ( J:201995 )

♂ • no abnormality in 1 month-old mice but byat 3 months, but not at 1 month, mutant mice displays spontaneous LV left ventricular systolic dysfunction.

abnormal myocardial fiber physiology ( J:201995 )

♂ • isolated cardiomyocytes fail to show a sustained increase in intracellular calcium following exposure to low concentrations of caffeine

pathological neovascularization ( J:201995 )

♂ • associated with atrial thrombosis

congestive heart failure ( J:201995 )

♂

heart inflammation ( J:201995 )

♂ • indicated by expression analysis

Genotype
MGI:5433520

cn94

• Allelic Composition: Hey2^tm2.1Mtc/Hey2^tm2.1Mtc; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6 * FVB/N * SJL

cardiovascular system

cardiac hypertrophy ( J:186570 )

• after pressure overload

cardiac fibrosis ( J:186570 )

• after pressure overload

decreased cardiac muscle contractility ( J:186570 )

• after pressure overload

• in cells from 12 week old mice

• however, treatment with FK506, an inhibitor of FKBP12.6, rescues defective cardiac function

abnormal myocardial fiber physiology ( J:186570 )

• cardiomyocytes exhibit altered calcium cycling compared with control mice

• however, calcium sensitivity and stores are normal and treatment with FK506, an inhibitor of FKBP12.6, rescues defective peak calcium release

increased response of heart to induced stress ( J:186570 )

• after pressure overload, mice exhibit increased cardiac hypertrophy, decreased fractional shortening, fibrosis and heart failure compared with control mice

congestive heart failure ( J:186570 )

• after pressure overload

• however, mice do not exhibit cardiac failure under normal conditions

homeostasis/metabolism

increased response of heart to induced stress ( J:186570 )

• after pressure overload, mice exhibit increased cardiac hypertrophy, decreased fractional shortening, fibrosis and heart failure compared with control mice

muscle

decreased cardiac muscle contractility ( J:186570 )

• after pressure overload

• in cells from 12 week old mice

• however, treatment with FK506, an inhibitor of FKBP12.6, rescues defective cardiac function

growth/size/body

cardiac hypertrophy ( J:186570 )

• after pressure overload

Genotype
MGI:3510548

cn95

• Allelic Composition: Map3k5^tm1Hijo/Map3k5^tm1Hijo; Raf1^tm2Bacc/Raf1^tm2Bacc; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J

cardiovascular system

cardiovascular system phenotype ( J:93418 )

N • heart size, morphology and function are not significantly different from wild-type unlike Raf1^tm2Bacc, Tg(Myhca-cre)2182Mds mutants

Genotype
MGI:3525858

cn96

• Allelic Composition: Mapk14^tm1.2Otsu/Mapk14^tm1.2Otsu; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:95116 )

• 30% of mutants died one week after TAC induced pressure overload compared to 8% in controls

cardiovascular system

enlarged heart ( J:95116 )

• heart was larger than in controls after TAC induced pressure overload or adrenergic stimulation

increased heart weight ( J:95116 )

• heart weight, left ventricle weight, and average ratio of left ventricle weight to tibial length or body weight were significantly greater than in controls after TAC induced pressure overload, however no difference in cardiomyocyte cell area was observed

cardiac fibrosis ( J:95116 )

• observed intermuscular and perivascular fibrosis in mutants compared to only slight perivascular fibrosis in controls after TAC induced pressure overload

decreased cardiac muscle contractility ( J:95116 )

• mice exhibit normal cardiac function and structure under baseline conditions, however cardiac contractility was significantly reduced after thoracic transverse aortic constriction (TAC) induced pressure overload and chronic adrenergic stimulation

decreased heart left ventricle muscle contractility ( J:95116 )

• increased left ventricle end-diastolic and end-systolic diameters compared to controls after TAC induced pressure overload

increased response of heart to induced stress ( J:95116 )

• after TAC induced pressure overload, exhibit greater increases in mortality, heart size and weight, cardiac fibrosis, and cardiomyocyte apoptosis and decreased cardiac contractility compared to controls

muscle

decreased cardiac muscle contractility ( J:95116 )

• mice exhibit normal cardiac function and structure under baseline conditions, however cardiac contractility was significantly reduced after thoracic transverse aortic constriction (TAC) induced pressure overload and chronic adrenergic stimulation

decreased heart left ventricle muscle contractility ( J:95116 )

• increased left ventricle end-diastolic and end-systolic diameters compared to controls after TAC induced pressure overload

increased cardiomyocyte apoptosis ( J:95116 )

• the number of apoptotic cardiac myocytes was 3.7 times that in controls after TAC induced pressure overload and was also increased in response to chronic adrenergic stimulation

homeostasis/metabolism

increased response of heart to induced stress ( J:95116 )

• after TAC induced pressure overload, exhibit greater increases in mortality, heart size and weight, cardiac fibrosis, and cardiomyocyte apoptosis and decreased cardiac contractility compared to controls

cellular

increased cardiomyocyte apoptosis ( J:95116 )

• the number of apoptotic cardiac myocytes was 3.7 times that in controls after TAC induced pressure overload and was also increased in response to chronic adrenergic stimulation

growth/size/body

enlarged heart ( J:95116 )

• heart was larger than in controls after TAC induced pressure overload or adrenergic stimulation

increased heart weight ( J:95116 )

• heart weight, left ventricle weight, and average ratio of left ventricle weight to tibial length or body weight were significantly greater than in controls after TAC induced pressure overload, however no difference in cardiomyocyte cell area was observed

Genotype
MGI:3510547

cn97

• Allelic Composition: Raf1^tm2Bacc/Raf1^tm2Bacc; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J

cardiovascular system

thin myocardium ( J:93418 )

• posterior wall thickness is significantly decreased

enlarged heart ( J:93418 )

• the heart is enlarged; however, heart weight is not increased

dilated heart left ventricle ( J:93418 )

cardiac fibrosis ( J:93418 )

decreased cardiac muscle contractility ( J:93418 )

• fractional shortening indicate that cardiac contractility is significantly decreased

decreased heart left ventricle muscle contractility ( J:93418 )

• reduced maximal and minimal first derivatives of left ventricular pressure indicate that cardiac contractility and relaxation are significantly decreased

muscle

thin myocardium ( J:93418 )

• posterior wall thickness is significantly decreased

decreased cardiac muscle contractility ( J:93418 )

• fractional shortening indicate that cardiac contractility is significantly decreased

decreased heart left ventricle muscle contractility ( J:93418 )

• reduced maximal and minimal first derivatives of left ventricular pressure indicate that cardiac contractility and relaxation are significantly decreased

increased cardiomyocyte apoptosis ( J:93418 )

• increased apoptosis in the heart is seen from 3-5 weeks of age but not at 2 weeks or after 6 weeks of age

cellular

increased cardiomyocyte apoptosis ( J:93418 )

• increased apoptosis in the heart is seen from 3-5 weeks of age but not at 2 weeks or after 6 weeks of age

growth/size/body

enlarged heart ( J:93418 )

• the heart is enlarged; however, heart weight is not increased

Genotype
MGI:5806895

cn98

• Allelic Composition: Cap2^{tm1c(EUCOMM)Wtsi}/Cap2^{tm1c(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J * C57BL/6N

mortality/aging

premature death ( J:234044 )

• males and females are born in equal numbers and appear healthy with no overt discomfort but exhibit sudden death by heart block between 12 and 24 weeks of age

• both males and females die at about the same age, indicating that there is no male bias in sudden death

cardiovascular system

cardiovascular system phenotype ( J:234044 )

N • at 12-20 weeks of age, no significant differences in left ventricular wall thickness, chamber size or function are observed in male or female mice relative to control mice

N • mice show no signs of increased interstitial fibrosis at ~15 weeks of age

decreased heart rate ( J:234044 )

• at 1 hour prior to death, mice exhibit a significantly lower heart rate than control mice

• average heart rate begins to drop at ~5 days prior to death

sinus bradycardia ( J:234044 )

• all (4 of 4) mice develop sinus bradycardia, unlike control mice which show no evidence of arrhythmias

abnormal impulse conducting system conduction ( J:234044 )

• at 12-20 weeks of age, mice show a significant increase in the AV Wenckebach cycle length relative to control mice

prolonged RR interval ( J:234044 )

• at 1 hour prior to death, mice show longer RR intervals than control mice

atrioventricular block ( J:234044 )

• all mice develop sinus bradycardia and die a few days later from complete atrioventricular block, unlike control mice which show no evidence of conduction defects or arrhythmias

prolonged HV interval ( J:234044 )

• at 12-20 weeks of age, mice show a significant increase in the HV-interval relative to control mice

prolonged QRS complex duration ( J:234044 )

• at 1 hour prior to death, mice show longer QRS intervals than control mice

Genotype
MGI:7662823

cn99

• Allelic Composition: Trim29^{tm1c(EUCOMM)Wtsi}/Trim29^{tm1c(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * C57BL/6NTac
• Cell Lines: EPD0439_4_D01

mortality/aging

decreased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:349246 )

♂ • following i.p. infection with Coxsackievirus B3 (CVB3, strain Nancy), mice show significantly improved survival rates relative to CVB3-infected controls

immune system

increased T cell proliferation ( J:349246 )

♂ • when myeloid-derived suppressor cells (MDSCs) from 3-day CVB3-infected hearts are cocultured with negatively selected CD3+ T cells and stimulated with anti-CD3 and anti-CD28 antibodies, the % of proliferating CD8+ T cells is significantly higher than that in controls

increased interferon level ( J:349246 )

♂ • following CVB3 infection, mice show significantly higher IFN-alpha and IFN-beta levels in the heart than CVB3-infected controls

decreased interleukin level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower IL-6 and IL-1beta levels in the heart than CVB3-infected controls

abnormal tumor necrosis factor level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower TNF levels in the heart than CVB3-infected controls

increased interferon-gamma secretion ( J:349246 )

♂ • upon in vitro stimulation with PMA/ionomycin, CD8+ T cells show a significantly enhanced IFN-gamma producing ability in the heart and spleen from 2-day CVB3-infected mice

♂ • however, the IFN-gamma-producing ability of CD8+ T cells in spleen is similar to that in untreated controls before CVB3 infection

decreased inflammatory response ( J:349246 )

♂ • 2 days after CVB3 infection, mice show significantly lower cell numbers of monocytic MDSCs (CD11b+Ly6C+Ly6G-), macrophages, neutrophils, B cells and T cells infiltrated in the heart than CVB3-infected controls

decreased susceptibility to Picornaviridae infection ( J:349246 )

♂ • following i.p. infection with Coxsackievirus B3 (CVB3, strain Nancy), mice show significantly less inflammation and infiltration of inflammatory cells in heart, lower heart weight/baseline body weight, improved cardiac function (as assessed by ejection fraction and fractional shortening), reduced viral titers in heart, pancreas and spleen homogenates, and lower levels of cardiac inflammatory cytokines (IL-6, IL-1beta, and TNF) than CVB3-infected controls, indicating protection from viral myocarditis

decreased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:349246 )

♂ • following i.p. infection with Coxsackievirus B3 (CVB3, strain Nancy), mice show significantly improved survival rates relative to CVB3-infected controls

cellular

decreased fetal cardiomyocyte apoptosis ( J:349246 )

♂ • in vitro, primary neonatal cardiomyocytes infected with CVB3 show dramatically reduced expression of CHOP, cleaved caspase-3, and BAX, indicating reduced EIF2AK3-mediated ER stress and apoptosis

increased T cell proliferation ( J:349246 )

♂ • when myeloid-derived suppressor cells (MDSCs) from 3-day CVB3-infected hearts are cocultured with negatively selected CD3+ T cells and stimulated with anti-CD3 and anti-CD28 antibodies, the % of proliferating CD8+ T cells is significantly higher than that in controls

decreased endoplasmic reticulum stress ( J:349246 )

♂ • following infection with CVB3, primary neonatal cardiomyocytes from 2-day-old mice show dramatically reduced phosphorylation of EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3, also known as PERK), suggesting reduced EIF2AK3-mediated ER stress

homeostasis/metabolism

decreased circulating creatine kinase level ( J:349246 )

♂ • following CVB3 infection, mice show dramatically reduced circulating creatine kinase levels relative to CVB3-infected controls

increased interferon level ( J:349246 )

♂ • following CVB3 infection, mice show significantly higher IFN-alpha and IFN-beta levels in the heart than CVB3-infected controls

decreased interleukin level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower IL-6 and IL-1beta levels in the heart than CVB3-infected controls

abnormal tumor necrosis factor level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower TNF levels in the heart than CVB3-infected controls

hematopoietic system

increased T cell proliferation ( J:349246 )

♂ • when myeloid-derived suppressor cells (MDSCs) from 3-day CVB3-infected hearts are cocultured with negatively selected CD3+ T cells and stimulated with anti-CD3 and anti-CD28 antibodies, the % of proliferating CD8+ T cells is significantly higher than that in controls

decreased myeloid cell number ( J:349246 )

♂ • 2 days after CVB3 infection, mice show a significantly lower frequency of myeloid-derived suppressor cells (CD11b+ Gr1+ MDSCs) in the heart and spleen than CVB3-infected controls

♂ • however, the frequency of MDSCs in spleen is similar to that in untreated controls before CVB3 infection

cardiovascular system

decreased fetal cardiomyocyte apoptosis ( J:349246 )

♂ • in vitro, primary neonatal cardiomyocytes infected with CVB3 show dramatically reduced expression of CHOP, cleaved caspase-3, and BAX, indicating reduced EIF2AK3-mediated ER stress and apoptosis

muscle

decreased fetal cardiomyocyte apoptosis ( J:349246 )

♂ • in vitro, primary neonatal cardiomyocytes infected with CVB3 show dramatically reduced expression of CHOP, cleaved caspase-3, and BAX, indicating reduced EIF2AK3-mediated ER stress and apoptosis

Genotype
MGI:6159290

cn100

• Allelic Composition: Nae1^{tm1c(EUCOMM)Wtsi}/Nae1^{tm1c(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/N * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:261328 )

• expected or near expected numbers are found at E18.5 and P1 but no pups survive past P7 with most dying around 48-72 h after birth

cardiovascular system

abnormal myocardium layer morphology ( J:261328 )

• marked increase in the left ventricular noncompaction to compaction ratio at P1

increased myocardial fiber size ( J:261328 )

• increase in cardiomyocyte cross-sectional area

myocardial hypertrabeculation ( J:261328 )

• thicker trabecular layer in the left ventricle at E16.5

myocardial ventricular hypertrabeculation ( J:261328 )

• hypertrabeculation at P1

• at P1 prominent trabeculae that deeply penetrate into the compact layer are seen in both ventricles

myocardium hypoplasia ( J:261328 )

• at P1

thin ventricle myocardium compact layer ( J:261328 )

• at P1 thinner in both left and right ventricles

thin left ventricle myocardium compact layer ( J:261328 )

• thinner in the left ventricle at E16.5

abnormal heart development ( J:261328 )

• impaired ventricular wall maturation

enlarged heart ( J:261328 )

increased heart weight ( J:261328 )

• increase in heart to body weight ratio

cardiac hypertrophy ( J:261328 )

decreased heart left ventricle wall thickness ( J:261328 )

• left ventricular wall thinning at E18.5 and P1

dilated heart left ventricle ( J:261328 )

• marked increase in both left ventricle systolic and diastolic diameters and decrease in left ventricle systolic wall thickness at P1

• dilation is seen at E18.5

dilated heart right ventricle ( J:261328 )

• dilation is seen at E18.5

decreased heart ventricle muscle contractility ( J:261328 )

• ejection fraction is reduced to 50% of controls

decreased fetal cardiomyocyte proliferation ( J:261328 )

• at E14.5 and E16.5

decreased heart rate ( J:261328 )

homeostasis/metabolism

cyanosis ( J:261328 )

• develops by 48-72 h post birth

extremity edema ( J:261328 )

• peripheral edema develops by 48-72 h post birth

cellular

decreased fetal cardiomyocyte proliferation ( J:261328 )

• at E14.5 and E16.5

muscle

abnormal myocardium layer morphology ( J:261328 )

• marked increase in the left ventricular noncompaction to compaction ratio at P1

increased myocardial fiber size ( J:261328 )

• increase in cardiomyocyte cross-sectional area

myocardial hypertrabeculation ( J:261328 )

• thicker trabecular layer in the left ventricle at E16.5

myocardial ventricular hypertrabeculation ( J:261328 )

• hypertrabeculation at P1

• at P1 prominent trabeculae that deeply penetrate into the compact layer are seen in both ventricles

myocardium hypoplasia ( J:261328 )

• at P1

thin ventricle myocardium compact layer ( J:261328 )

• at P1 thinner in both left and right ventricles

thin left ventricle myocardium compact layer ( J:261328 )

• thinner in the left ventricle at E16.5

decreased heart ventricle muscle contractility ( J:261328 )

• ejection fraction is reduced to 50% of controls

decreased fetal cardiomyocyte proliferation ( J:261328 )

• at E14.5 and E16.5

growth/size/body

enlarged heart ( J:261328 )

increased heart weight ( J:261328 )

• increase in heart to body weight ratio

cardiac hypertrophy ( J:261328 )

Genotype
MGI:5792710

cn101

• Allelic Composition: Snrk^tm2Rra/Snrk^tm2Rra; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J * FVB/N

mortality/aging

mortality/aging ( J:218247 )

N • mice do not exhibit neonatal lethality unlike knock-out mice

premature death ( J:218247 )

• mice die between 8 to 10 months of age

cardiovascular system

cardiovascular system phenotype ( J:218247 )

N • mice exhibit normal stroke volume, left ventricle mass and heart rate

abnormal heart left ventricle morphology ( J:218247 )

• enlarged left ventricle inner diameter in systole and diastole

• increased end diastolic and end systolic volume

decreased heart left ventricle muscle contractility ( J:218247 )

• decreased ejection fraction and fractional shortening in the left ventricle

homeostasis/metabolism

abnormal lipid level ( J:218247 )

• neonatal hearts exhibit increased staining for neutral lipids using oil red O (ORO)

muscle

decreased heart left ventricle muscle contractility ( J:218247 )

• decreased ejection fraction and fractional shortening in the left ventricle

Genotype
MGI:5792711

cn102

• Allelic Composition: Snrk^tm2Rra/Snrk⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J * FVB/N

mortality/aging

premature death ( J:218247 )

• mice die shortly after one year of age

Genotype
MGI:5293311

cn103

• Allelic Composition: Capns1^tm1.1Otsu/Capns1^tm1.1Otsu; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J * FVB/N

Increased cardiac fibrosis in Capns1^tm1.1Otsu/Capns1^tm1.1Otsu Tg(Myh6-cre)2182Mds/0 mice after transverse aortic constriction

cardiovascular system

abnormal heart left ventricle morphology ( J:176736 )

• in response to pressure overload or isoproterenol treatment, mice exhibit increased end-diastolic and end-systolic LV internal dimension compared with similarly treated wild-type mice

dilated heart left ventricle ( J:176736 )

• 2 weeks after isoproterenol treatment

cardiac fibrosis ( J:176736 )

• in response to pressure overload

decreased cardiac muscle contractility ( J:176736 )

• in response to pressure overload or isoproterenol treatment

abnormal myocardial fiber physiology ( J:176736 )

• mice exposed to pressure overload exhibit plasma membrane in heart sarcolemma compared with similarly treated wild-type mice

• heart sarcolemma exhibit defective membrane damage repair compared with similarly treated wild-type mice

increased response of heart to induced stress ( J:176736 )

• in response to pressure overload, mice exhibit congestive heart failure (increased end-diastolic and end-systolic LV internal dimension, decreased fractional shortening, and increased lung weight to body weight) compared with similarly treated wild-type mice

• mice treated with isoproterenol exhibit congestive heart failure (increased end-diastolic and end-systolic LV internal dimension, decreased fractional shortening, increased heart weight, and increased lung weight to body weight) compared with similarly treated wild-type mice

congestive heart failure ( J:176736 )

• in response to pressure overload or isoproterenol treatment

respiratory system

increased lung weight ( J:176736 )

• in response to pressure overload or isoproterenol treatment

homeostasis/metabolism

increased response of heart to induced stress ( J:176736 )

• in response to pressure overload, mice exhibit congestive heart failure (increased end-diastolic and end-systolic LV internal dimension, decreased fractional shortening, and increased lung weight to body weight) compared with similarly treated wild-type mice

• mice treated with isoproterenol exhibit congestive heart failure (increased end-diastolic and end-systolic LV internal dimension, decreased fractional shortening, increased heart weight, and increased lung weight to body weight) compared with similarly treated wild-type mice

muscle

decreased cardiac muscle contractility ( J:176736 )

• in response to pressure overload or isoproterenol treatment

growth/size/body

increased lung weight ( J:176736 )

• in response to pressure overload or isoproterenol treatment

Genotype
MGI:7596339

cn104

• Allelic Composition: Mtfp1^tm1.2Wait/Mtfp1^tm1.2Wait; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6N * FVB/N

mortality/aging

premature death ( J:330965 )

• significantly shorter lifespans, 26.4 weeks and 37.5 weeks for males and females, respectively

cardiovascular system

pulmonary vascular congestion ( J:330965 )

• in mice with severe heart failure

enlarged heart ( J:330965 )

• increased mass in mice with severe heart failure

abnormal heart ventricle morphology ( J:330965 )

thin interventricular septum ( J:330965 )

• thinning during systole

dilated heart left ventricle ( J:330965 )

• during diastole and systole

thin ventricular wall ( J:330965 )

• wall thinning at 34 weeks of age

cardiac fibrosis ( J:330965 )

• in symptomatic mice

dilated cardiomyopathy ( J:330965 )

• progressive decrease in systolic function starting at 18 weeks of age culminating in dilated cardiomyopathy and left ventricular remodeling

decreased heart left ventricle muscle contractility ( J:330965 )

• decreased left ventricular ejection fraction by 34 weeks of age

• prior to onset of cardiomyopathy (8-10 weeks of age) no significant difference in cardiomyocyte excitation-contraction coupling is seen

cellular

increased cardiomyocyte apoptosis ( J:330965 )

• increased cell death when exposed to H2O2 or doxorubicin in culture and to doxorubicin in vivo

abnormal mitochondrial physiology ( J:330965 )

• impaired mitochondrial O2 consumption in hearts at early and late stages of dilated cardiomyopathy

• significant reduction in complex I-, complex II- and complex IV-driven mitochondrial respiration

• no changes in mitochondrial protein content or markers of mitochondrial metabolic activity in pre-symptomatic mice

• respiration is about 30% higher in cardiac mitochondria in state 2 and state 4 when complex 1 is fueled by pyruvate, malate, glutamate

• results indicate increase in proton leak in cardiac cells

• increased mitochondrial swelling in response to high concentrations of Ca2+ induced opening of the mitochondrial permeability transition pore

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:330965 )

• increased cardiac dysfunction and acceleration of the onset of cardiomyopathy in response to doxorubicin

growth/size/body

enlarged heart ( J:330965 )

• increased mass in mice with severe heart failure

respiratory system

pulmonary vascular congestion ( J:330965 )

• in mice with severe heart failure

muscle

dilated cardiomyopathy ( J:330965 )

• progressive decrease in systolic function starting at 18 weeks of age culminating in dilated cardiomyopathy and left ventricular remodeling

decreased heart left ventricle muscle contractility ( J:330965 )

• decreased left ventricular ejection fraction by 34 weeks of age

• prior to onset of cardiomyopathy (8-10 weeks of age) no significant difference in cardiomyocyte excitation-contraction coupling is seen

increased cardiomyocyte apoptosis ( J:330965 )

• increased cell death when exposed to H2O2 or doxorubicin in culture and to doxorubicin in vivo

Genotype
MGI:7378415

cn105

• Allelic Composition: Acad9^{tm1c(KOMP)Wtsi}/Acad9^{tm1c(KOMP)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6N * FVB/N

mortality/aging

postnatal lethality ( J:326969 )

• mice begin to die shortly after P14, with the earliest death at P13 and die by P17

cardiovascular system

abnormal heart morphology ( J:326969 )

• the respiratory chain supercomplexes and isolated complex I are absent in hearts

myocardial fiber disarray ( J:326969 )

thick ventricular wall ( J:326969 )

decreased cardiac muscle contractility ( J:326969 )

• ejection fraction is reduced by as much as 27-fold and is already reduced at P3

cardiomyopathy ( J:326969 )

• mice exhibit dramatic cardiomyopathy with thickening of the atrial and ventricular walls and severe enlargement of all chambers

• cardiomyopathy is already seen at P3

cellular

abnormal mitochondrial physiology ( J:326969 )

• mitochondria do not respond to substrates that drive complex I (malate, pyruvate, and glutamate) but have a normal response to the complex II substrate succinate

• mitochondria also show no response to injection of rotenone which leads to loss of respiration in wild-type mitochondria

muscle

myocardial fiber disarray ( J:326969 )

decreased cardiac muscle contractility ( J:326969 )

• ejection fraction is reduced by as much as 27-fold and is already reduced at P3

cardiomyopathy ( J:326969 )

• mice exhibit dramatic cardiomyopathy with thickening of the atrial and ventricular walls and severe enlargement of all chambers

• cardiomyopathy is already seen at P3

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nuclear type mitochondrial complex I deficiency 20		DOID:0112072	OMIM:611126	J:326969

Genotype
MGI:3655840

cn106

• Allelic Composition: Lpl^tm1Ijg/Lpl^tm1Ijg; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

Increase in interstitial and perivascular collagen in Lpl^tm1Ijg/Lpl^tm1Ijg Tg(Myh6-cre)2182Mds/0 hearts

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:110484 )

• all mutants subjected to abdominal aortic constriction (AbAC) die within 2 days whereas controls survive

cardiovascular system

cardiac fibrosis ( J:110484 )

• hearts from non-stressed 4-5 month old males, but not females, show increased fibrosis as indicated by Trichrome staining; fibrosis is both interstitial and perivascular

cardiac interstitial fibrosis ( J:110484 )

• seen in non-stressed 4-5 month old males

abnormal cardiovascular system physiology ( J:110484 )

• hearts from both 4-5 month old males and females exhibit higher rates of glycolysis and glucose oxidation

• palmitate oxidation rates in male and female hearts are reduced by 52 and 40%, respectively, indicating reduction in fatty acid utilization

• heart uptake of VLDL triglycerides is decreased by 49% and uptake of palmitate, a free fatty acid, is increased by 56% in females

• male, but not female, hearts show a reduction in cardiac power

increased cardiac muscle cell glucose uptake ( J:110484 )

• myocardial basal glucose uptake is increased 5.5-fold

decreased heart left ventricle muscle contractility ( J:110484 )

• 6-month old mutants exhibit an increase in left ventricular systolic dimension and a decrease in fractional shortening under basal conditions

increased left ventricle diastolic pressure ( J:110484 )

• mutants subjected to abdominal aortic constriction exhibit an increase in left ventricular end diastolic pressure that is not observed in banded controls

increased left ventricle systolic pressure ( J:110484 )

• mutants subjected to abdominal aortic constriction exhibit a greater increase in left ventricular systolic pressure than banded controls

homeostasis/metabolism

increased circulating triglyceride level ( J:110484 )

• 4 month old females show elevated plasma triglyceride levels, however plasma cholesterol, free fatty acid, and glucose levels are normal

abnormal glucose homeostasis ( J:110484 )

• hearts from both 4-5 month old males and females exhibit higher rates of glycolysis and glucose oxidation

muscle

increased cardiac muscle cell glucose uptake ( J:110484 )

• myocardial basal glucose uptake is increased 5.5-fold

decreased heart left ventricle muscle contractility ( J:110484 )

• 6-month old mutants exhibit an increase in left ventricular systolic dimension and a decrease in fractional shortening under basal conditions

cellular

cardiac interstitial fibrosis ( J:110484 )

• seen in non-stressed 4-5 month old males

increased cardiac muscle cell glucose uptake ( J:110484 )

• myocardial basal glucose uptake is increased 5.5-fold

Genotype
MGI:3639277

cn107

• Allelic Composition: Gata4^tm1.1Wtp/Gata4^tm1.1Wtp; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:99203 )

• lethality by E14.5

cardiovascular system

double outlet right ventricle ( J:99203 )

heart hypoplasia ( J:99203 )

• marked myocardial hyperplasia

abnormal fetal cardiomyocyte proliferation ( J:99203 )

• reduction in cardiomyocyte proliferation

muscle

abnormal fetal cardiomyocyte proliferation ( J:99203 )

• reduction in cardiomyocyte proliferation

cellular

abnormal fetal cardiomyocyte proliferation ( J:99203 )

• reduction in cardiomyocyte proliferation

Genotype
MGI:6275067

cn108

• Allelic Composition: Tg(ACTB-EGFP,-Kcnj8*)1Wco/0; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

cardiovascular system

abnormal myocardial fiber morphology ( J:134852 )

• isolated ventricular myocytes lack functional ATP-sensitive K⁺ channels

muscle

abnormal myocardial fiber morphology ( J:134852 )

• isolated ventricular myocytes lack functional ATP-sensitive K⁺ channels

Genotype
MGI:5543777

cn109

• Allelic Composition: Ehmt1^tm2Yshk/Ehmt1^tm2Yshk; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

normal phenotype

no abnormal phenotype detected ( J:204470 )

• mice are born, develop and show no apparent abnormalities in appearance, cardiogenesis or fertility

Genotype
MGI:5314604

cn110

• Allelic Composition: Tg(CAG-cat,-TBX3)1Vmc/0; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

cardiovascular system

myocardium hypoplasia ( J:181526 )

• mice exhibit hypoplastic chamber walls with reduced cellular proliferation in the ventricular walls compared to in control mice

ventricle myocardium hypoplasia ( J:181526 )

abnormal heart development ( J:181526 )

• mice exhibit a subendocardial space near the atrioventricular cushions filled with mesenchymal cells unlike in control mice

• mice exhibit abnormal cardiac jelly and cushion formation in chamber myocardium compared with control mice

muscle

myocardium hypoplasia ( J:181526 )

• mice exhibit hypoplastic chamber walls with reduced cellular proliferation in the ventricular walls compared to in control mice

ventricle myocardium hypoplasia ( J:181526 )

Genotype
MGI:5319195

cn111

• Allelic Composition: Fkbp1a^tm1.1Shou/Fkbp1a^tm1.1Shou; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

cardiovascular system

abnormal heart electrocardiography waveform feature ( J:183588 )

• shorter PP interval

• significant acceleration of the maximal phase 0 upstroke velocity in the left ventricle

abnormal myocardial fiber physiology ( J:183588 )

• mean peak macroscopic voltage-gated Na+ current densities are increased more than 2 fold in ventricular cardiomyocytes

• acceleration of both the early and late component of voltage-gated Na+ current inactivation in ventricular cardiomyocytes

Genotype
MGI:6766588

cn112

• Allelic Composition: Hand1^tm5Abfi/Hand1⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

mortality/aging

lethality during fetal growth through weaning, incomplete penetrance ( J:311466 )

• expected numbers of embryos are obtained at E10.5 and E14.5 but reduced numbers of neonates are seen at P1

cardiovascular system

abnormal heart apex morphology ( J:311466 )

• hearts lack a well-defined apex at P60

cardiac hypertrophy ( J:311466 )

• bifurcated hearts appear slightly hypertrophied at P60

• however, cardiac morphology appears normal at E14.5

growth/size/body

cardiac hypertrophy ( J:311466 )

• bifurcated hearts appear slightly hypertrophied at P60

• however, cardiac morphology appears normal at E14.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	hypoplastic left heart syndrome	DOID:9955	OMIM:241550 OMIM:614435	J:311466

Genotype
MGI:3696414

cn113

• Allelic Composition: Map3k7^tm1Mds/Map3k7^tm1Mds; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:117108 )

• lethality in midgestation, at the same time as seen in Map3k7^{Gt(Betageo-ALPP)1Byg} homozygotes

Genotype
MGI:4461321

cn114

• Allelic Composition: Tg(CAG-Map3k7*K63W)1232Mds/0; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:117108 )

• die by 11 days after birth

cardiovascular system

increased cardiac muscle glycogen level ( J:117108 )

• cardiomyocyte glycogen content is elevated in hearts at 7 days of age

abnormal heart morphology ( J:117108 )

• disruption of the annulus fibrosus

abnormal myocardial fiber morphology ( J:117108 )

• myocyte hypertrophy as indicated by increased myocyte diameter and induction of hypertrophic marker genes

abnormal ventricle papillary muscle morphology ( J:117108 )

• develop papillary muscle disorganization and fibrosis

• papillary muscle dysplasia

cardiac hypertrophy ( J:117108 )

• heart-to-body weight ratio is normal at birth but is doubled by 7 days of age

thin ventricular wall ( J:117108 )

• invariably develop ventricular wall thinning

dilated heart ventricle ( J:117108 )

• develop ventricular dilatation

abnormal cardiovascular system physiology ( J:117108 )

• exhibit severely impaired ventricular filling and regurgitant flow into the left atrium

shortened PR interval ( J:117108 )

• PR interval shortening is evident at 1 day after birth and is further shortened by 4-8 days of age, indicating shortened AV conduction time

abnormal QRS complex ( J:117108 )

• ventricular QRS complex is initially normal, but all develop a slurred widened QRS morphology with an initial delta wave by 4-8 days of age

prolonged QRS complex duration ( J:117108 )

cardiomyopathy ( J:117108 )

• glycogen storage cardiomyopathy

growth/size/body

cardiac hypertrophy ( J:117108 )

• heart-to-body weight ratio is normal at birth but is doubled by 7 days of age

periorbital edema ( J:117108 )

postnatal growth retardation ( J:117108 )

• become growth retarded within 1 week after birth

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:117108 )

• cardiomyocyte glycogen content is elevated in hearts at 7 days of age

periorbital edema ( J:117108 )

abnormal atrial thrombosis ( J:117108 )

• develop left atrial thrombi

behavior/neurological

decreased locomotor activity ( J:117108 )

• exhibit decreased activity

muscle

increased cardiac muscle glycogen level ( J:117108 )

• cardiomyocyte glycogen content is elevated in hearts at 7 days of age

abnormal myocardial fiber morphology ( J:117108 )

• myocyte hypertrophy as indicated by increased myocyte diameter and induction of hypertrophic marker genes

abnormal ventricle papillary muscle morphology ( J:117108 )

• develop papillary muscle disorganization and fibrosis

• papillary muscle dysplasia

cardiomyopathy ( J:117108 )

• glycogen storage cardiomyopathy

craniofacial

periorbital edema ( J:117108 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Wolff-Parkinson-White syndrome		DOID:384	OMIM:194200	J:117108

Genotype
MGI:3812382

cn115

• Allelic Composition: Cxadr^tm1Mgot/Cxadr^tm1Mgot; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:140109 )

• embryonic lethality occurs between E11.5 and E12.5

Genotype
MGI:3051890

cn116

• Allelic Composition: Gja1^tm1Gfi/Gja1^tm1Gfi; Tg(Myh6-cre)2182Mds/0
• Genetic Background: Not Specified

mortality/aging

premature death ( J:91971 )

• begin to die at 2-3 weeks of age and all are dead within the first 2 months

cardiovascular system

increased heart rate ( J:91971 )

• abrupt tachyarrhythmia develop which could not be terminated by high frequency pacing in 6 out of 10 mice

• degenerates to ventricular fibrillation

Genotype
MGI:2651646

cn117

• Allelic Composition: Ttn^tm1Her/Ttn^tm1Her; Tg(Myh6-cre)2182Mds/0
• Genetic Background: Not Specified

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:81993 )

• resorbed embryos were observed at E15; none are found at birth

Genotype
MGI:5526034

tg118

• Allelic Composition: Tg(Myh6-cre)2182Mds/0
• Genetic Background: Not Specified

cardiovascular system

cardiovascular system phenotype ( J:201995 )

N • normal echocardiograms at up to 6 mo of age