Phenotypes associated with this allele

• Allele Symbol: Tg(Tek-cre)12Flv
• Allele Name: transgene insertion 12, Richard A Flavell
• Allele ID: MGI:2136412
• Summary: 89 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Adam17^tm1.1Rain/Adam17^tm1.2Rain Tg(Tek-cre)12Flv/0	B6.Cg-Adam17^tm1.1Rain Adam17^tm1.2Rain Tg(Tek-cre)12Flv	MGI:5478754
cn2	Adgra2^tm1.1Bstc/Adgra2^tm1.2Bstc Tg(Tek-cre)12Flv/0	B6.Cg-Adgra2^tm1.1Bstc/Adgra2^tm1.2Bstc Tg(Tek-cre)12Flv	MGI:4949906
cn3	Ahr^tm3.1Bra/Ahr^tm3.1Bra Tg(Tek-cre)12Flv/0	B6.Cg-Ahr^tm3.1Bra Tg(Tek-cre)12Flv	MGI:3613532
cn4	Capn1^tm1Ahc/Capn1^tm1Ahc Capn2^tm2.1Tcs/Capn2^tm2.1Tcs Tg(Tek-cre)12Flv/0	B6.Cg-Capn2^tm2.1Tcs Capn1^tm1Ahc Tg(Tek-cre)12Flv	MGI:5292743
cn5	Fli1^tm1Matr/Fli1^tm1Matr Tg(Tek-cre)12Flv/0	B6.Cg-Fli1^tm1Matr Tg(Tek-cre)12Flv	MGI:4441385
cn6	Fli1^tm1Matr/Fli1^tm1Matr Tg(Tek-cre)12Flv/Tg(Tek-cre)12Flv	B6.Cg-Fli1^tm1Matr Tg(Tek-cre)12Flv	MGI:4441395
cn7	Lypla1^tm1Sem/Lypla1^tm1Sem Tg(Tek-cre)12Flv/0	B6(Cg)-Lypla1^tm1Sem Tg(Tek-cre)12Flv	MGI:6514417
cn8	Mcam^tm1Yanx/Mcam^tm1Yanx Tg(Tek-cre)12Flv/0	B6.Cg-Mcam^tm1Yanx Tg(Tek-cre)12Flv	MGI:5445421
cn9	Plvap^tm1.1Rvst/Plvap^tm1.1Rvst Tg(Tek-cre)12Flv/0	B6.Cg-Plvap^tm1.1Rvst Tg(Tek-cre)12Flv	MGI:5473522
cn10	Pparg^tm2Rev/Pparg^tm2Rev Tg(Tek-cre)12Flv/?	B6.Cg-Pparg^tm2Rev Tg(Tek-cre)12Flv	MGI:5444197
cn11	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan Tg(Tek-cre)12Flv/0	B6.Cg-Rb1cc1^tm1.1Guan Tg(Tek-cre)12Flv	MGI:4936843
cn12	Tfpi^tm1.1Rdsi/Tfpi^tm1.1Rdsi Tg(Tek-cre)12Flv/0	B6.Cg-Tfpi^tm1.1Rdsi Tg(Tek-cre)12Flv	MGI:4836841
cn13	Slc7a5^tm1.1Daca/Slc7a5^tm1.1Daca Tg(Tek-cre)12Flv/0	B6J.Cg-Slc7a5^tm1.1Daca Tg(Tek-cre)12Flv	MGI:5829465
cn14	Stat3^tm1Flv/Stat3^tm1Flv Tg(Tek-cre)12Flv/0	involves: 129 * C3H * C57BL/6	MGI:3783296
cn15	Notch1^tm1Agt/Notch1^tm1Agt Tg(Tek-cre)12Flv/0	involves: 129 * C3H * C57BL/6	MGI:3710256
cn16	Pdcd10^tm1Wami/Pdcd10^tm1Wami Tg(Tek-cre)12Flv/0	involves: 129 * C3H * C57BL/6	MGI:5002664
cn17	Map3k7^tm1Aki/Map3k7^tm1Aki Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * 129S2/SvPas * C3H * C57BL/6	MGI:5464102
cn18	Calcrl^tm1Kmca/Calcrl^tm2Kmca Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J	MGI:3772943
cn19	Map3k7^tm1Aki/Map3k7^tm1Aki Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:5464101
cn20	Rbpj^tm1Kyo/Rbpj^tm1Hon Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:3056465
cn21	Stat3^tm1Aki/Stat3^tm1Aki Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:3796175
cn22	Mib1^tm2Kong/Mib1^tm2Kong Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:3804815
cn23	Tab2^tm2.1Aki/Tab2^tm2.1Aki Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:5464103
cn24	Tab2^tm2.1Aki/Tab2^tm2.1Aki Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:5464104
cn25	Tg(CAG-Bgeo,-Hras1,-EGFP)#Ichi/0 Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:4821337
cn26	Ptk2^tm1.1Guan/Ptk2^tm1.1Guan Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:4820573
cn27	Cxcr4^tm1Tng/Cxcr4^tm2Tng Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:5502187
cn28	Tg(CAG-Bgeo,-tsA58T)T26Ichi/0 Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:4442226
cn29	Ptk2^tm1.1Guan/Ptk2^tm1.2Guan Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6 * C57BL/6J	MGI:3583921
cn30	Ercc1^tm1Jhjh/Ercc1^tm3Jhjh Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N	MGI:5553270
cn31	Ptk2^tm2.1Guan/Ptk2^tm1.1Guan Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N	MGI:4820572
cn32	Dlk1^tm1.1Jvs/Dlk1^+ Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N	MGI:5471939
cn33	Acvr1^tm1Vk/Acvr1^tm1.1Vk Tg(Tek-cre)12Flv/0	involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6	MGI:3697608
cn34	Sox17^tm1Sjm/Sox17^tm2Sjm Tg(Tek-cre)12Flv/0	involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6 * C57BL/Ka	MGI:3717920
cn35	Gba1^tm1Clk/Gba1^tm1.1Clk Tg(Tek-cre)12Flv/0	involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6J	MGI:3699178
cn36	Vcam1^tm2Flv/Vcam1^tm3Flv Tg(Tek-cre)12Flv/0	involves: 129S1/Sv * C3H * C57BL/6	MGI:3845662
cn37	Ddah1^tm1Yjch/Ddah1^tm1Yjch Tg(Tek-cre)12Flv/0	involves: 129S1/Sv * C57BL/6J	MGI:4887353
cn38	Gipc1^tm1.1Mhsi/Gipc1^tm1.1Mhsi Tg(Tek-cre)12Flv/?	involves: 129S1/SvImJ * 129S4/SvJaeSor * C3H * C57BL/6	MGI:5696327
cn39	Nostrin^tm1Oess/Nostrin^tm1Oess Tg(Tek-cre)12Flv/0	involves: 129S2/SvPas * C3H * C57BL/6	MGI:5444445
cn40	Mapk1^tm1Melo/Mapk1^+ Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: 129S2/SvPas * C3H * C57BL/6 * FVB/N	MGI:3822161
cn41	Mir92-1^tm1Sdim/Mir92-1^tm1Sdim Tg(Tek-cre)12Flv/0	involves: 129S2/SvPas * C3H * C57BL/6J	MGI:5706726
cn42	Plvap^tm1.1Rvst/Plvap^tm1.1Rvst Tg(Tek-cre)12Flv/0	involves: 129S4/SvJae * C3H * C57BL/6	MGI:5473521
cn43	Kras^tm4Tyj/Kras^+ Tg(Tek-cre)12Flv/0	involves: 129S4/SvJae * C3H * C57BL/6	MGI:3716393
cn44	Adgrf5^tm1.1Bstc/Adgrf5^tm1.2Bstc Tg(Tek-cre)12Flv/0	involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6J	MGI:5490533
cn45	Tfpi^tm1.1Rdsi/Tfpi^tm1.1Rdsi Tg(Tek-cre)12Flv/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * BALB/cJ * C3H * C57BL/6	MGI:4836837
cn46	Ate1^tm2.1Akas/Ate1^tm2.1Akas Tg(Tek-cre)12Flv/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C3H * C57BL/6 * CD-1	MGI:4414850
cn47	Gt(ROSA)26Sor^tm1(Wnk1)Clhu/Gt(ROSA)26Sor^+ Wnk1^Gt(OST38262)Lex/Wnk1^Gt(OST38262)Lex Tg(Tek-cre)12Flv/0	involves: 129S5/SvEvBrd * C3H * C57BL/6	MGI:4360980
cn48	Metap2^tm1.1Ccr/Metap2^tm1.1Ccr Tg(Tek-cre)12Flv/0	involves: 129S6/SvEvTac * C3H * C57BL/6	MGI:3663893
cn49	Ptpn11^tm6Bgn/Ptpn11^+ Tg(Tek-cre)12Flv/0	involves: 129S6/SvEvTac * C3H * C57BL/6	MGI:3840254
cn50	Zfx^tm1.1Reiz/Y Tg(Tek-cre)12Flv/0	involves: 129S6/SvEvTac * C3H * C57BL/6	MGI:3848804
cn51	Kitl^tm1.1Sjm/Kitl^tm2.1Sjm Lepr^tm2(cre)Rck/Lepr^+ Tg(Tek-cre)12Flv/0	involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/Ka * SJL	MGI:5306357
cn52	Ppp2ca^tm1.1Nju/Ppp2ca^tm1.1Nju Tg(Tek-cre)12Flv/0	involves: 129S6/SvEvTac * C57BL/6	MGI:4950916
cn53	Tab1^tm1Mis/Tab1^tm1Mis Tg(Tek-cre)12Flv/0	involves: 129S7/SvEvBrd * C3H * C57BL/6	MGI:5464105
cn54	Agtr1a^tm1Uky/Agtr1a^tm1Uky Ldlr^tm1Her/Ldlr^tm1Her Tg(Tek-cre)12Flv/0	involves: 129S7/SvEvBrd * C3H * C57BL/6 * C57BL/6N	MGI:4946112
cn55	Efnb2^tm1And/Efnb2^tm2And Tg(Tek-cre)12Flv/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:2176622
cn56	Ackr3^tm1Twb/Ackr3^tm1.1Twb Tg(Tek-cre)12Flv/0	involves: 129S/SvEv * BALB/cJ * C3H * C57BL/6	MGI:4881715
cn57	Mir21a^tm1.1Zqy/Mir21a^tm1.1Zqy Tg(Tek-cre)12Flv/0	involves: 129S/SvEv * C3H * C57BL/6 * SJL	MGI:5514138
cn58	Adgra2^tm1Cjku/Adgra2^tm2Cjku Tg(Tek-cre)12Flv/0	involves: 129/Sv * C3H * C57BL/6	MGI:4840270
cn59	Mapk3^tm1Gpg/Mapk3^+ Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: 129/Sv * C3H * C57BL/6 * FVB/N	MGI:3822163
cn60	Mapk3^tm1Gpg/Mapk3^tm1Gpg Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: 129/Sv * C3H * C57BL/6 * FVB/N	MGI:3822162
cn61	Smo^tm2Amc/Smo^tm2Amc Tg(Tek-cre)12Flv/0	involves: 129X1/SvJ * C3H * C57BL/6	MGI:5563907
cn62	H2-Ab1^b-tm1Koni/H2-Ab1^b-tm1.1Koni Tg(Tek-cre)12Flv/0	involves: 129X1/SvJ * C3H * C57BL/6 * C57BL/6J	MGI:5285614
cn63	H2-Ab1^b-tm1.1Koni/H2-Ab1^b-tm1.1Koni Tg(Tek-cre)12Flv/0	involves: 129X1/SvJ * C3H * C57BL/6 * C57BL/6J	MGI:5285615
cn64	Smo^tm2Amc/Smo^tm2.1Amc Tg(Tek-cre)12Flv/0	involves: 129X1/SvJ * C57BL/6	MGI:4843921
cn65	Kitl^tm2.1Sjm/Kitl^tm2.2Sjm Tg(Tek-cre)12Flv/0	involves: BALB/cJ * C3H * C57BL/6 * C57BL/Ka * SJL	MGI:5306355
cn66	Hspd1^tm1c(EUCOMM)Hmgu/Hspd1^tm1c(EUCOMM)Hmgu Tg(Tek-cre)12Flv/0	involves: Black Swiss * C3H * C57BL/6 * C57BL/6N	MGI:6385861
cn67	Klf2^tm1Mlkn/Klf2^tm1Mlkn Tg(Tek-cre)12Flv/?	involves: C3H * C57BL/6	MGI:3765432
cn68	Smad7^tm1Shou/Smad7^tm1Shou Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6	MGI:3839597
cn69	Nus1^tm1Wcsa/Nus1^tm1Wcsa Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6	MGI:6361094
cn70	Il1r1^tm1Quan/Il1r1^tm1Quan Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6	MGI:5634707
cn71	Wnk1^tm1Clhu/Wnk1^tm1Clhu Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6	MGI:4360979
cn72	Cxcl12^tm1.1Sjm/Cxcl12^tm1.1Sjm Tg(Tek-cre)12Flv/?	involves: C3H * C57BL/6	MGI:5488609
cn73	Jag1^tm2Grid/Jag1^tm2Grid Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6	MGI:4867008
cn74	Ccl2^tm1.1Pame/Ccl2^tm1.1Pame Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6	MGI:4950281
cn75	Ackr3^tm1Fma/Ackr3^tm1Fma Tg(Tek-cre)12Flv/?	involves: C3H * C57BL/6	MGI:3723119
cn76	Bmal1^tm2Bra/Bmal1^tm2Bra Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * C57BL/6J	MGI:4822129
cn77	Pkn2^tm1c(KOMP)Wtsi/Pkn2^tm1c(KOMP)Wtsi Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * C57BL/6N	MGI:5912009
cn78	Creld1^tm1c(EUCOMM)Wtsi/Creld1^tm1c(EUCOMM)Wtsi Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * C57BL/6N * SJL	MGI:7546786
cn79	Mecom^tm1Miku/Mecom^+ Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * CBA	MGI:3849427
cn80	Mecom^tm1Miku/Mecom^tm1Miku Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * CBA	MGI:3849426
cn81	Tg(CAG-cat,-Ptpn11)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * FVB/N	MGI:3822159
cn82	Tg(ACTB-EGFP,-Kcnj8*)1Wco/0 Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * FVB/N	MGI:6275068
cn83	Tg(CAG-cat,-Map2k1*)243Rbns/0 Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * FVB/N	MGI:3822160
cn84	Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * FVB/N	MGI:3822157
cn85	Pdia4^tm1b(EUCOMM)Wtsi/Pdia4^tm1b(EUCOMM)Wtsi Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6N	MGI:6157438
cn86	Lman1^tm1c(KOMP)Wtsi/Lman1^tm1c(KOMP)Wtsi Tg(Tek-cre)12Flv/0	involves: C57BL/6 * C57BL/6J * C57BL/6N	MGI:5607596
cn87	Piezo1^tm1c(KOMP)Wtsi/Piezo1^tm1c(KOMP)Wtsi Tg(Tek-cre)12Flv/0	involves: C57BL/6J * C57BL/6N	MGI:5824010
cn88	Mapk7^tm1Jdl/Mapk7^tm1Jdl Tg(Tek-cre)12Flv/0	Not Specified	MGI:3042042
tg89	Tg(Tek-cre)12Flv/Tg(Tek-cre)12Flv	involves: C3H * C57BL/6	MGI:4414849

Genotype
MGI:5478754

cn1

• Allelic Composition: Adam17^tm1.1Rain/Adam17^tm1.2Rain; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Adam17^tm1.1Rain Adam17^tm1.2Rain Tg(Tek-cre)12Flv

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:195050 )

• under represented by 75% at weaning but found at the expected frequency at E18.5

cardiovascular system

increased heart weight ( J:195050 )

• cardiomegaly occurs postnatally as heart to body mass ratio is similar to controls at E18.5

abnormal semilunar valve morphology ( J:195050 )

• enlarged at E18.5

• valve cusps appear hyperplastic with a 43% increase in the median number of cells and 57% increase in thickness

• increase in thickness is persistent in adults

• however, unlike in global null mice atrioventricular valve leaflets are not overtly abnormal

abnormal aortic valve cusp morphology ( J:195050 )

• the glycosaminoglycan/proteoglycan-rich spongiosa layer of the extracellular matrix is enlarged with increased space between the granules

• 9 of 13 mutants have at least one cusp with aberrant localization and/or excessive levels of collagen

thick aortic valve cusps ( J:195050 )

aortic valve stenosis ( J:195050 )

• in surviving adults

enlarged semilunar valve ( J:195050 )

• at E18.5

increased heart left ventricle size ( J:195050 )

♀ • increase in left ventricular end diastolic dimension in females at 24 to 28 weeks of age

increased heart left ventricle weight ( J:195050 )

• increase in heart size is primarily due to expansion of the left ventricle

decreased cardiac muscle contractility ( J:195050 )

• decrease in ejection fraction ad fractional shortening in males and females at 24 to 28 weeks of age

abnormal aortic valve flow ( J:195050 )

♀ • increase in aortic valve peak velocity in females at 24 to 28 weeks of age

increased heart rate ( J:195050 )

♀ • at 24 to 28 weeks of age in females

muscle

decreased cardiac muscle contractility ( J:195050 )

• decrease in ejection fraction ad fractional shortening in males and females at 24 to 28 weeks of age

growth/size/body

increased heart weight ( J:195050 )

• cardiomegaly occurs postnatally as heart to body mass ratio is similar to controls at E18.5

Genotype
MGI:4949906

cn2

• Allelic Composition: Adgra2^tm1.1Bstc/Adgra2^tm1.2Bstc; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Adgra2^tm1.1Bstc/Adgra2^tm1.2Bstc Tg(Tek-cre)12Flv

cardiovascular system

abnormal brain vasculature morphology ( J:171226 )

• at E12.5 glomeruloid bodies form in the lateral ventricle wall in the region adjacent to the ganglionic eminence, similar to what is seen in Gpr124^tm1.2Bstc homozygotes

intracranial hemorrhage ( J:171226 )

spinal hemorrhage ( J:171226 )

nervous system

abnormal brain vasculature morphology ( J:171226 )

• at E12.5 glomeruloid bodies form in the lateral ventricle wall in the region adjacent to the ganglionic eminence, similar to what is seen in Gpr124^tm1.2Bstc homozygotes

intracranial hemorrhage ( J:171226 )

spinal hemorrhage ( J:171226 )

abnormal telencephalon development ( J:171226 )

• failure of neocortex development

abnormal pallium development ( J:171226 )

• notably thinner at E15.5

Genotype
MGI:3613532

cn3

• Allelic Composition: Ahr^tm3.1Bra/Ahr^tm3.1Bra; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Ahr^tm3.1Bra Tg(Tek-cre)12Flv

cardiovascular system

patent ductus venosus ( J:104388 )

• 18 of 22 mutants retain a patent ductus venosus as adults

cellular

patent ductus venosus ( J:104388 )

• 18 of 22 mutants retain a patent ductus venosus as adults

Genotype
MGI:5292743

cn4

• Allelic Composition: Capn1^tm1Ahc/Capn1^tm1Ahc; Capn2^tm2.1Tcs/Capn2^tm2.1Tcs; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Capn2^tm2.1Tcs Capn1^tm1Ahc Tg(Tek-cre)12Flv

normal phenotype

no abnormal phenotype detected ( J:175868 )

• viable with no significant abnormalities detected for at least 1 year

Genotype
MGI:4441385

cn5

• Allelic Composition: Fli1^tm1Matr/Fli1^tm1Matr; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Fli1^tm1Matr Tg(Tek-cre)12Flv

cardiovascular system

abnormal blood vessel morphology ( J:158658 )

• dermal vasculature is disorganized with irregular vessel diameters unlike in wild-type mice

• dermal capillaries, arterioles, and venules exhibit increased vessel diameter compared to in wild-type mice

abnormal arteriole morphology ( J:158658 )

• dermal capillaries, arterioles, and venules exhibit increased vessel diameter compared to in wild-type mice

• arterioles exhibit a 65% increase in endothelial cells and pericytes compared to in wild-type mice

increased vascular endothelial cell number ( J:158658 )

• arterioles exhibit a 65% increase in endothelial cells and pericytes compared to in wild-type mice

• however, endothelial cell proliferation or apoptosis rates are normal

dilated capillary ( J:158658 )

• capillaries are dilated in the skin vascular network compared to in wild-type mice

• dermal capillaries, arterioles, and venules exhibit increased vessel diameter compared to in wild-type mice

abnormal pericyte morphology ( J:158658 )

• arterioles exhibit a 65% increase in endothelial cells and pericytes compared to in wild-type mice

• pericyte/vascular smooth muscle cell coverage is decreased compared to in wild-type mice

abnormal vascular smooth muscle morphology ( J:158658 )

• pericyte/vascular smooth muscle cell coverage is decreased compared to in wild-type mice

abnormal venule morphology ( J:158658 )

• dermal capillaries, arterioles, and venules exhibit increased vessel diameter compared to in wild-type mice

vascular stenosis ( J:158658 )

• in arterioles of dermal vascular networks

aneurysm ( J:158658 )

• microaneurysms are observed in the skin vascular network compared with wild-type mice

hemorrhage ( J:158658 )

• mice are more hemorrhagic against mechanical force such as cervical dislocation and surgical procedure compared with similarly treated wild-type mice

increased vascular permeability ( J:158658 )

• skin vasculature on the ears and back exhibits increased permeability compared with wild-type mice

• skin vascular leakage is more severe when ears are treated with mineral oil compared with wild-type ears treated with mustard oil

growth/size/body

decreased body weight ( J:158658 )

• from P3 until 3 months of age

muscle

abnormal vascular smooth muscle morphology ( J:158658 )

• pericyte/vascular smooth muscle cell coverage is decreased compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic scleroderma		DOID:418	OMIM:181750	J:158658

Genotype
MGI:4441395

cn6

• Allelic Composition: Fli1^tm1Matr/Fli1^tm1Matr; Tg(Tek-cre)12Flv/Tg(Tek-cre)12Flv
• Genetic Background: B6.Cg-Fli1^tm1Matr Tg(Tek-cre)12Flv

mortality/aging

perinatal lethality, incomplete penetrance ( J:158658 )

prenatal lethality, complete penetrance ( J:158658 )

• fewer than expected mice are produced likely due to some embryonic and early perinatal loss

Genotype
MGI:6514417

cn7

• Allelic Composition: Lypla1^tm1Sem/Lypla1^tm1Sem; Tg(Tek-cre)12Flv/0
• Genetic Background: B6(Cg)-Lypla1^tm1Sem Tg(Tek-cre)12Flv

cardiovascular system

abnormal aorta morphology ( J:302677 )

• aortas have increased soluble and insoluble fibronectin

abnormal physiological neovascularization ( J:302677 )

• mice subjected to femoral artery ligation (model of peripheral artery disease) show decreased restoration of limb perfusion, with reduced vessel area and smaller lumen size of arteries, indicating decreased arteriogenesis

• mice subjected to femoral artery ligation show decreased pericyte coverage of microvascular networks, indicating decreased angiogenesis

• 2 weeks after femoral artery ligation, fibronectin is increased in the intima, but not the media, of lower extremity arteries

abnormal vascular endothelial cell physiology ( J:302677 )

• primary endothelial cells exhibit increased F-actin stress fibers, increased cell-matrix adhesions, and increased cell spreading

• adherens junctions are reduced in confluent endothelial cells

• the ratio of insoluble/soluble fibronectin is decreased in aortic endothelial cells and turnover of fibronectin is decreased, indicating decreased maturation of fibronectin matrix

abnormal vascular endothelial cell adhesion ( J:302677 )

• primary endothelial cells coated on microbeads embedded in fibrin gel give rise to tree-like structures with broken branches and isolated cells unlike control cells, indicating altered cell adhesion

cellular

abnormal vascular endothelial cell adhesion ( J:302677 )

• primary endothelial cells coated on microbeads embedded in fibrin gel give rise to tree-like structures with broken branches and isolated cells unlike control cells, indicating altered cell adhesion

Genotype
MGI:5445421

cn8

• Allelic Composition: Mcam^tm1Yanx/Mcam^tm1Yanx; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Mcam^tm1Yanx Tg(Tek-cre)12Flv

cardiovascular system

decreased angiogenesis ( J:189203 )

• VEGF-induced in Matrigel

Genotype
MGI:5473522

cn9

• Allelic Composition: Plvap^tm1.1Rvst/Plvap^tm1.1Rvst; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Plvap^tm1.1Rvst Tg(Tek-cre)12Flv

mortality/aging

preweaning lethality, complete penetrance ( J:191046 )

• Background Sensitivity: display 100% lethality by P2 on a congenic C57BL/6 background unlike mice on a mixed background where about 20-30% of mice survive to 3-4 months of age

Genotype
MGI:5444197

cn10

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Tek-cre)12Flv/?
• Genetic Background: B6.Cg-Pparg^tm2Rev Tg(Tek-cre)12Flv

growth/size/body

decreased body weight ( J:154216 )

• about 5% less than controls

enlarged spleen ( J:154216 )

immune system

enlarged spleen ( J:154216 )

hematopoietic system

enlarged spleen ( J:154216 )

decreased hematocrit ( J:154216 )

• slightly reduced hematocrit

cardiovascular system

increased mean systemic arterial blood pressure ( J:154216 )

• higher baseline pressure

• greater increase when challenged with angiotensin II

abnormal vascular endothelial cell physiology ( J:154216 )

• reduced NO production in blood vessel endothelium

abnormal vasodilation ( J:154216 )

• impaired endothelium dependent acetylcholine mediated relaxation of aortic rings

muscle

abnormal vasodilation ( J:154216 )

• impaired endothelium dependent acetylcholine mediated relaxation of aortic rings

impaired muscle relaxation ( J:154216 )

• impaired endothelium dependent acetylcholine mediated relaxation of aortic rings

Genotype
MGI:4936843

cn11

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Rb1cc1^tm1.1Guan Tg(Tek-cre)12Flv

mortality/aging

postnatal lethality, complete penetrance ( J:167258 )

• all mice die within the first week of birth

lethality throughout fetal growth and development, incomplete penetrance ( J:167258 )

• slight decrease in the number of expected embryos observed at E17.5 and E18.5

hematopoietic system

increased hematopoietic stem cell proliferation ( J:167258 )

• hematopoietic stem cells (HSCs) exhibit increased rate of proliferation, but no differences in apoptosis, compared to wild-type HSCs

abnormal erythropoiesis ( J:167258 )

• fetal erythropoiesis is impaired in mutants by E16.5, with very few erythrocytes within vascular structures

• at E14.5, marker analysis indicates that mutants exhibit an increase in frequency of immature erythroid cells and a reduction in the absolute number of maturing erythroid cells, suggesting that erythroid maturation is compromised

abnormal myelopoiesis ( J:167258 )

• E14.5 fetal liver exhibits a more than 4-fold increase in the number of myeloid lineage cells, indicating enhanced myelopoiesis

anemia ( J:167258 )

• severe erythroblastic anemia

increased erythroblast number ( J:167258 )

• increase in numbers of erythroblasts in the peripheral blood at E18.5

decreased erythrocyte cell number ( J:167258 )

• at E18.5

decreased hematocrit ( J:167258 )

• at E18.5

decreased hemoglobin content ( J:167258 )

• at E18.5

increased red blood cell distribution width ( J:167258 )

• at E18.5

increased neutrophil cell number ( J:167258 )

• in peripheral blood at E18.5

decreased hematopoietic stem cell number ( J:167258 )

• 6-fold lower frequency of immunophenotypic HSCs in fetal livers at E14.5; competitive reconstitution experiments confirm the reduction in HSCs and that HSCs simply do not change their immunephenotype in mut

liver/biliary system

abnormal liver morphology ( J:167258 )

• decrease in total fetal liver cell number at E14.5, with further decreases at E18.5

pale liver ( J:167258 )

• at E16.5 and E18.5

cellular

abnormal mitochondrial morphology ( J:167258 )

• fetal liver cells at E14.5 exhibit an increase in mitochondrial mass

abnormal autophagy ( J:167258 )

• mutants exhibit an accumulation of p62, a selective substrate for autophagy, and a 50% increase in ROS levels in fetal cells, indicating a defect in autophagy in fetal liver cells

increased hematopoietic stem cell proliferation ( J:167258 )

• hematopoietic stem cells (HSCs) exhibit increased rate of proliferation, but no differences in apoptosis, compared to wild-type HSCs

immune system

abnormal myelopoiesis ( J:167258 )

• E14.5 fetal liver exhibits a more than 4-fold increase in the number of myeloid lineage cells, indicating enhanced myelopoiesis

increased neutrophil cell number ( J:167258 )

• in peripheral blood at E18.5

cardiovascular system

cardiovascular system phenotype ( J:167258 )

N • hemorrhaging is not observed even though the cre transgene is expressed in endothelial cells

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:167258 )

N • edema is not observed even though the cre transgene is expressed in endothelial cells

abnormal autophagy ( J:167258 )

• mutants exhibit an accumulation of p62, a selective substrate for autophagy, and a 50% increase in ROS levels in fetal cells, indicating a defect in autophagy in fetal liver cells

Genotype
MGI:4836841

cn12

• Allelic Composition: Tfpi^tm1.1Rdsi/Tfpi^tm1.1Rdsi; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Tfpi^tm1.1Rdsi Tg(Tek-cre)12Flv

homeostasis/metabolism

abnormal circulating protein level ( J:164530 )

• decreased tissue factor pathway inhibitor protein level and activity

Genotype
MGI:5829465

cn13

• Allelic Composition: Slc7a5^tm1.1Daca/Slc7a5^tm1.1Daca; Tg(Tek-cre)12Flv/0
• Genetic Background: B6J.Cg-Slc7a5^tm1.1Daca Tg(Tek-cre)12Flv

homeostasis/metabolism

abnormal translation ( J:238065 )

• polysome profiling of brain cortical lysates showed a significant shift of ribosomes from actively translating polysomes toward the monosomal fraction, indicating decreased mRNA translation initiation in the brain

abnormal amino acid level ( J:238065 )

• after birth (P2-P14) and in adult stages (>P40), brain levels of branched-chain amino acids (BCAAs), esp. leucine and isoleucine, are abnormally low while levels of a few other amino acids (e.g., histidine, serine, and phenylalanine) are increased relative to those in age-matched controls

• brain histidine levels are several fold higher than in control mice

• brain levels of leucine and isoleucine are normalized after 3 weeks of intracerebroventricular (i.c.v.) BCAA (leucine and isoleucine) delivery

• brain levels of several other large neutral amino acids (LNAAs) including tyrosine and tryptophan are relatively normal, and serum amino acid levels are unchanged

• no major changes in brain LNAA and BCAA levels are noted at E14.5

increased phenylalanine level ( J:238065 )

• brain levels of phenylalanine are increased

increased serine level ( J:238065 )

• brain serine levels are modestly but significantly increased

abnormal amino acid metabolism ( J:238065 )

• mice show abnormal activation of the amino acid response (AAR) signal transduction pathway in the brain

behavior/neurological

abnormal behavior ( J:238065 )

• at P55-P65, mice exhibit motor delay and autism-like phenotypes

• some neurobehavioral phenotypes can be rescued by i.c.v. administration of leucine and isoleucine in adulthood

• mice do not show excessive grooming or stereotyped behavior in the marble burying test

limb grasping ( J:238065 )

• 89% of mice display hind limb clasping

• fewer mice (50%) show clasping after 3 weeks of i.c.v. BCAA delivery

impaired coordination ( J:238065 )

• mice show increased latency to cross the beam in the walking beam test

abnormal gait ( J:238065 )

• in the footprint test, mice show decreased stride and stance length and increased sway length relative to controls

• gait is improved after 3 weeks of i.c.v. BCAA delivery with complete normalization of the sway length

short stride length ( J:238065 )

decreased vertical activity ( J:238065 )

• rearing is significantly reduced

• number of rearings is normalized after 3 weeks of i.c.v. BCAA delivery

decreased locomotor activity ( J:238065 )

• mice show reduced explorative behavior and lower velocity in an open field test

• open field activity is normalized after 3 weeks of i.c.v. BCAA delivery

abnormal social investigation ( J:238065 )

• in the three chamber sociability test, P55-P65 mice fail to show preference for an unfamiliar caged wild-type mouse over a caged object, unlike controls

• in the juvenile social interaction test, P25-P35 mice tend to stay farther apart from their cage mate and show fewer nose-to-nose contacts than controls

excessive vocalization ( J:238065 )

• in the isolation-induced ultrasonic vocalization test, pups separated from the mother emit an increased number of calls starting at P8

motor developmental delay ( J:238065 )

• at P55-P65, mice exhibit motor delay

skeleton

kyphosis ( J:238065 )

• 44% of mice display kyphosis

• fewer mice (25%) show kyphosis after 3 weeks of i.c.v. BCAA delivery

nervous system

nervous system phenotype ( J:238065 )

N • brain neurotransmitter levels (dopamine, serotonin, histamine) are normal

abnormal synaptic bouton morphology ( J:238065 )

• EM imaging of somatosensory cortex layers 2-3 revealed a decreased area of GABAergic boutons and decreased density of vesicles per bouton

abnormal inhibitory synapse morphology ( J:238065 )

• the intensity of vesicular GABA transporter (VGAT) staining, a marker for GABAergic presynaptic terminals, is reduced in the somatosensory cortex

• however, protein levels the GABAergic postsynaptic marker neuroligin 2 are normal

abnormal symmetric synapse morphology ( J:238065 )

• mice show a significant reduction of vesicle number in symmetric synapses in the somatosensory cortex

abnormal synaptic vesicle number ( J:238065 )

• mice show a significant reduction of vesicle number in symmetric synapses in the somatosensory cortex

abnormal CNS synaptic transmission ( J:238065 )

• mice exhibit a significant cortical excitation and inhibition imbalance

abnormal miniature excitatory postsynaptic currents ( J:238065 )

• mice show a slight increase in the amplitude of mEPSCs in somatosensory cortex layers 2-3 pyramidal neurons

decreased miniature inhibitory postsynaptic current frequency ( J:238065 )

• mice show a marked reduction in the frequency of mIPSCs in somatosensory cortex layers 2-3 pyramidal neurons as well as in cerebellar Purkinje cells

cellular

abnormal translation ( J:238065 )

• polysome profiling of brain cortical lysates showed a significant shift of ribosomes from actively translating polysomes toward the monosomal fraction, indicating decreased mRNA translation initiation in the brain

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:238065

Genotype
MGI:3783296

cn14

• Allelic Composition: Stat3^tm1Flv/Stat3^tm1Flv; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129 * C3H * C57BL/6

Crohn's disease-like pathogenesis in Stat3^tm1Flv/Stat3^tm1Flv Tg(Tek-cre)12Flv/0 mice

mortality/aging

premature death ( J:81973 )

• die within 4-6 weeks after birth, and none survive more than 8 weeks

growth/size/body

decreased body size ( J:81973 )

• mutants are smaller at 3-4 weeks of age

decreased body weight ( J:81973 )

• reduced body weight is seen at 3-4 weeks of age

behavior/neurological

weakness ( J:81973 )

• mutants appear fragile and weak by 4-6 weeks of age

immune system

increased leukocyte cell number ( J:81973 )

• bone marrow shows an expansion of GR-1+Mac1+ neutrophil lineage (20% in controls vs. 35% in mutants), indicating an abnormal expansion of a myeloid lineage in the bone marrow

• lethally irradiated recipients of mutant bone marrow show much higher numbers of attached Mac1+ cells than controls and mutant bone marrow cultured in the presence of CSF-1 shows an increase in the generation of attached macrophages than controls indicating cell autonomous overproduction of myeloid cells

abnormal T-helper 1 physiology ( J:81973 )

• deregulated T helper 1-type immune response

increased circulating interferon-gamma level ( J:81973 )

increased circulating tumor necrosis factor level ( J:81973 )

• increase in TNF-alpha levels

abnormal inflammatory response ( J:81973 )

intestinal inflammation ( J:81973 )

• massive infiltration of the intestine with neutrophils, macrophages, and eosinophils

• myeloid cells, rather than lymphocytes, are the major cell populations in the inflammatory infiltrates of the gastrointestinal tract

cecum inflammation ( J:81973 )

• a transmural inflammation of all layers of the cecum is observed

colitis ( J:81973 )

• a transmural inflammation of all layers of the colon is observed

ileum inflammation ( J:81973 )

• transmural inflammation

granulomatous inflammation ( J:81973 )

• granuloma-like structures in the ileocecal area

liver inflammation ( J:81973 )

• the liver shows infiltration of granulocytes around the portal vein

abnormal innate immunity ( J:81973 )

• mutants show overly pseudoactivated innate immune responses

digestive/alimentary system

abnormal intestine morphology ( J:81973 )

• intestine shows ulceration, bowel wall thickening, granuloma formation, and segmental inflammatory cell infiltration

intestinal ulcer ( J:81973 )

abnormal cecum morphology ( J:81973 )

• ulceration and a transmural inflammation of all layers of the cecum is observed

• cecum exhibits crypt abscesses with necrotic neutrophils and monocytes, high frequency of mitosis in the epithelium, edema of the lamina propria and epithelioid cells with eosinophilic cytoplasm

abnormal colon morphology ( J:81973 )

• colon of 4-week old mutants shows bowel wall thickening, mucosal erosion, transmural inflammation affecting all layers, edema in the submucosa, and serosa thickening

abnormal ileum morphology ( J:81973 )

• ileum is fused to the peritoneal wall in severely sick mutants

• ileum shows ulceration, loss of mucosal texture, transmural inflammation, granuloma-like structures and abnormal changes in the mucosa, submucosa, smooth muscle and serosa

intestinal inflammation ( J:81973 )

• massive infiltration of the intestine with neutrophils, macrophages, and eosinophils

• myeloid cells, rather than lymphocytes, are the major cell populations in the inflammatory infiltrates of the gastrointestinal tract

cecum inflammation ( J:81973 )

• a transmural inflammation of all layers of the cecum is observed

colitis ( J:81973 )

• a transmural inflammation of all layers of the colon is observed

ileum inflammation ( J:81973 )

• transmural inflammation

hematopoietic system

increased leukocyte cell number ( J:81973 )

• bone marrow shows an expansion of GR-1+Mac1+ neutrophil lineage (20% in controls vs. 35% in mutants), indicating an abnormal expansion of a myeloid lineage in the bone marrow

• lethally irradiated recipients of mutant bone marrow show much higher numbers of attached Mac1+ cells than controls and mutant bone marrow cultured in the presence of CSF-1 shows an increase in the generation of attached macrophages than controls indicating cell autonomous overproduction of myeloid cells

abnormal T-helper 1 physiology ( J:81973 )

• deregulated T helper 1-type immune response

homeostasis/metabolism

increased circulating interferon-gamma level ( J:81973 )

increased circulating tumor necrosis factor level ( J:81973 )

• increase in TNF-alpha levels

decreased NAD(P)H oxidase activity ( J:81973 )

• NADPH oxidase activity of neutrophils is reduced to 45% compared to more than 90% in controls

liver/biliary system

liver inflammation ( J:81973 )

• the liver shows infiltration of granulocytes around the portal vein

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:81973

Genotype
MGI:3710256

cn15

• Allelic Composition: Notch1^tm1Agt/Notch1^tm1Agt; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129 * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:100449 )

• die at around E10.5

growth/size/body

embryonic growth retardation ( J:100449 )

• embryos show a pronounced delay in posterior development, with some showing incomplete embryonic turning

embryo

abnormal placental labyrinth vasculature morphology ( J:100449 )

• blood vessels fail to invade the placental labyrinth

incomplete embryo turning ( J:100449 )

• seen in some embryos

embryonic growth arrest ( J:100449 )

• at E9.5, embryos display growth arrest at the 16-to 20-somite stage

embryonic growth retardation ( J:100449 )

• embryos show a pronounced delay in posterior development, with some showing incomplete embryonic turning

neural tube degeneration ( J:100449 )

• the forebrain neural tube is degenerated, with abundant pyknotic and fragmented nuclei

abnormal somite development ( J:100449 )

• somites are poorly defined, with signs of apoptosis

abnormal vitelline vascular remodeling ( J:100449 )

• embryos fail to remodel the primary vascular plexus to form large and small blood vessels of the mature yolk sac

cardiovascular system

abnormal intersomitic vessel morphology ( J:100449 )

• intersomitic blood vessels are poorly defined, with signs of apoptosis

abnormal placental labyrinth vasculature morphology ( J:100449 )

• blood vessels fail to invade the placental labyrinth

abnormal angiogenesis ( J:100449 )

• exhibit a marked reduction in vessel organization and a persistent, immature vascular plexus, suggesting a block in vascular maturation and angiogenic remodeling

• intact vasculogenesis but impaired secondary angiogenic sprouting and remodeling

abnormal vascular branching morphogenesis ( J:100449 )

• embryos show a decreased number of branching blood vessels throughout the embryo

abnormal anterior cardinal vein morphology ( J:100449 )

• the anterior cardinal vein appears hypoplastic

thin myocardium ( J:100449 )

delayed heart looping ( J:100449 )

• the heart displays delayed looping beginning at E9.5

pericardial effusion ( J:100449 )

• pericardial effusion is seen at E9.5 but not earlier

hemorrhage ( J:100449 )

• starting at E9.5, there is intraembryonic hemorrhage into the pericardium and tails

hemopericardium ( J:100449 )

• starting at E9.5, there is intraembryonic hemorrhage into the pericardium

nervous system

neural tube degeneration ( J:100449 )

• the forebrain neural tube is degenerated, with abundant pyknotic and fragmented nuclei

cellular

increased apoptosis ( J:100449 )

• widespread apoptosis in neural cells and the inner endothelial lining of the aorta

homeostasis/metabolism

pericardial effusion ( J:100449 )

• pericardial effusion is seen at E9.5 but not earlier

hemopericardium ( J:100449 )

• starting at E9.5, there is intraembryonic hemorrhage into the pericardium

muscle

thin myocardium ( J:100449 )

Genotype
MGI:5002664

cn16

• Allelic Composition: Pdcd10^tm1Wami/Pdcd10^tm1Wami; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129 * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:171969 )

• normal Mendelian ratios cannot be detected after E9.5

• no mice are present after E10.5

cardiovascular system

abnormal brain vasculature morphology ( J:171969 )

• mice exhibit abnormal angiogenesis and remodeling in the telencephalic plexus compared with wild-type mice

abnormal intersomitic vessel morphology ( J:171969 )

• intersomitic vessels are poorly organized and less branched compared to in wild-type mice

abnormal angiogenesis ( J:171969 )

• mice exhibit abnormal angiogenesis and remodeling in the yolk sac, telencephalic plexus, and intersomitic vasculature compared with wild-type mice

• angiogenesis is delayed compared to in wild-type mice

abnormal dorsal aorta morphology ( J:171969 )

• disorganized and discontinued

dilated dorsal aorta ( J:171969 )

abnormal developmental vascular remodeling ( J:171969 )

• mice exhibit abnormal angiogenesis and remodeling in the yolk sac, telencephalic plexus, and intersomitic vasculature compared with wild-type mice

abnormal vascular branching morphogenesis ( J:171969 )

abnormal cardinal vein morphology ( J:171969 )

• dilated, disorganized, and discontinued

abnormal vitelline vasculature morphology ( J:171969 )

• mice exhibit abnormal angiogenesis and remodeling in the yolk sac compared with wild-type mice

• the yolk sac contains fewer blood vessels compared to in wild-type mice

abnormal myocardium layer morphology ( J:171969 )

• the endocardium is dissociated from the myocardium unlike in wild-type mice

myocardial trabeculae hypoplasia ( J:171969 )

thin myocardium ( J:171969 )

abnormal endocardium morphology ( J:171969 )

• the endocardium is dissociated from the myocardium unlike in wild-type mice

enlarged pericardium ( J:171969 )

hematopoietic system

anemia ( J:171969 )

• at E8.5

impaired hematopoiesis ( J:171969 )

nervous system

nervous system phenotype ( J:171969 )

N • neural tube closure is normal

abnormal brain vasculature morphology ( J:171969 )

• mice exhibit abnormal angiogenesis and remodeling in the telencephalic plexus compared with wild-type mice

embryo

abnormal vitelline vasculature morphology ( J:171969 )

• mice exhibit abnormal angiogenesis and remodeling in the yolk sac compared with wild-type mice

• the yolk sac contains fewer blood vessels compared to in wild-type mice

abnormal vitelline vascular remodeling ( J:171969 )

muscle

abnormal myocardium layer morphology ( J:171969 )

• the endocardium is dissociated from the myocardium unlike in wild-type mice

myocardial trabeculae hypoplasia ( J:171969 )

thin myocardium ( J:171969 )

integument

pallor ( J:171969 )

• at E8.5

growth/size/body

microcephaly ( J:171969 )

Genotype
MGI:5464102

cn17

• Allelic Composition: Map3k7^tm1Aki/Map3k7^tm1Aki; Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:191285 )

• mice die by E13.5

cardiovascular system

cardiovascular system phenotype ( J:191285 )

N • blood vessels do not exhibit regression and exhibit normal vessel length and branching

dilated vasculature ( J:191285 )

cellular

cellular phenotype ( J:191285 )

N • embryonic endothelial cell apoptosis is rescued

Genotype
MGI:3772943

cn18

• Allelic Composition: Calcrl^tm1Kmca/Calcrl^tm2Kmca; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:130930 )

• mice die by E16.5

homeostasis/metabolism

edema ( J:130930 )

• at E13.5, mice exhibit interstitial edema without hemorrhage

Genotype
MGI:5464101

cn19

• Allelic Composition: Map3k7^tm1Aki/Map3k7^tm1Aki; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:191285 )

• mice die between E10.5 and E11.5

cardiovascular system

cardiovascular system phenotype ( J:191285 )

N • mice exhibit normal cardiac development

abnormal vascular development ( J:191285 )

• defective vascular development at E10.5 with disorganized vasculature and truncated capillary vessels

• however, development of the aorta is normal

decreased angiogenesis ( J:191285 )

• impaired vessel sprouting

abnormal vitelline vasculature morphology ( J:191285 )

• fewer vessel branches

embryo

abnormal vitelline vasculature morphology ( J:191285 )

• fewer vessel branches

cellular

increased apoptosis ( J:191285 )

• in embryonic endothelial cell

Genotype
MGI:3056465

cn20

• Allelic Composition: Rbpj^tm1Kyo/Rbpj^tm1Hon; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

cardiovascular system

abnormal dorsal aorta morphology ( J:93125 )

• the diameter of the dorsal aorta is reduced at E9.5

abnormal vascular regression ( J:93125 )

• at E9.5 PECAM-1 staining revealed a complete lack of vascular remodeling

abnormal anterior cardinal vein morphology ( J:93125 )

• the distal outflow tract is connected to the anterior cardinal vein by an anastamoses

abnormal common cardinal vein morphology ( J:93125 )

• some embryos also have more caudal fusions of the dorsal aorta to the common cardinal vein

absent vitelline blood vessels ( J:93125 )

• an avascular yolk is seen at E9.5

arteriovenous malformation ( J:93125 )

pericardial effusion ( J:93125 )

• pericardial effusion is seen at E9.5

embryo

absent vitelline blood vessels ( J:93125 )

• an avascular yolk is seen at E9.5

embryonic growth retardation ( J:93125 )

• embryonic growth retardation is seen at E9.5

growth/size/body

embryonic growth retardation ( J:93125 )

• embryonic growth retardation is seen at E9.5

homeostasis/metabolism

pericardial effusion ( J:93125 )

• pericardial effusion is seen at E9.5

cellular

abnormal vascular regression ( J:93125 )

• at E9.5 PECAM-1 staining revealed a complete lack of vascular remodeling

Genotype
MGI:3796175

cn21

• Allelic Composition: Stat3^tm1Aki/Stat3^tm1Aki; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

homeostasis/metabolism

abnormal interleukin level ( J:123351 )

• activated T_H cells from mutants produce no Il-21, Il-17, Il-17F or Il-22

immune system

abnormal interleukin level ( J:123351 )

• activated T_H cells from mutants produce no Il-21, Il-17, Il-17F or Il-22

Genotype
MGI:3804815

cn22

• Allelic Composition: Mib1^tm2Kong/Mib1^tm2Kong; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:130369 )

• mice die at around E11.5

embryo

absent vitelline blood vessels ( J:130369 )

• at E9.5 and E10.5

embryonic growth retardation ( J:130369 )

• at E9.5 and E10.5

abnormal vitelline vascular remodeling ( J:130369 )

• at E9.5 and E10.5, mice exhibit defects characteristic of vascular remodeling

cardiovascular system

cardiovascular system phenotype ( J:130369 )

N • despite defects in vascular remodeling, vasculogenesis is normal

abnormal dorsal aorta morphology ( J:130369 )

• the dorsal aorta is narrower than in wild-type mice and arterial specification is abnormal

abnormal vascular regression ( J:130369 )

• capillary networks are less extensive and more primitive than in wild-type mice

absent vitelline blood vessels ( J:130369 )

• at E9.5 and E10.5

pericardial effusion ( J:130369 )

• at E9.5 and E10.5

hematopoietic system

abnormal definitive hematopoiesis ( J:137915 )

• cultures of para-aortic splanchnopleura produce fewer colony forming cells when cultured alone or on OP9 cells compared to cultured wild-type cells

growth/size/body

embryonic growth retardation ( J:130369 )

• at E9.5 and E10.5

homeostasis/metabolism

pericardial effusion ( J:130369 )

• at E9.5 and E10.5

cellular

abnormal vascular regression ( J:130369 )

• capillary networks are less extensive and more primitive than in wild-type mice

Genotype
MGI:5464103

cn23

• Allelic Composition: Tab2^tm2.1Aki/Tab2^tm2.1Aki; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:191285 )

• mice die at E12.5

cardiovascular system

abnormal vascular development ( J:191285 )

• as in Map3k7^tm1Aki/Map3k7^tm1Aki Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak Tg(Tek-cre)12Flv mice

• however, endothelial cell proliferation and apoptosis rates are normal

abnormal vitelline vasculature morphology ( J:191285 )

• yolk sacs exhibit lagoon-like and less-branched vessel structures compared with control mice

embryo

abnormal vitelline vasculature morphology ( J:191285 )

• yolk sacs exhibit lagoon-like and less-branched vessel structures compared with control mice

Genotype
MGI:5464104

cn24

• Allelic Composition: Tab2^tm2.1Aki/Tab2^tm2.1Aki; Tnfrsf1a^tm1Mak/Tnfrsf1a^tm1Mak; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:191285 )

• mice die by E14.5

cardiovascular system

abnormal vascular development ( J:191285 )

• as in Tab2^tm2.1Aki/Tab2^tm2.1Aki Tg(Tek-cre)12Flv mice

Genotype
MGI:4821337

cn25

• Allelic Composition: Tg(CAG-Bgeo,-Hras1,-EGFP)#Ichi/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:159024 )

• mice die between E14.5 and E16.5

cardiovascular system

cardiovascular system phenotype ( J:159024 )

N • arteries and veins develop normally

homeostasis/metabolism

edema ( J:159024 )

• severe cutaneous edema at E15.5

immune system

lymphatic vessel hyperplasia ( J:159024 )

• in the skin

Genotype
MGI:4820573

cn26

• Allelic Composition: Ptk2^tm1.1Guan/Ptk2^tm1.1Guan; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:162690 )

• fewer mutant embryos than Mendelian ratio at E13.5

• no live mutant embryos at E14.5

cellular

increased apoptosis ( J:162690 )

• increased apoptosis in the liver, brain, placenta and skin at E13.5

• presence of apoptotic endothelial cells (ECs) in the blood vessel of the brain and skin

• increased apoptosis after recombinant adenoviruses encoding Cre (Ad-Cre) infection of the ECs in vitro

growth/size/body

decreased embryo size ( J:162690 )

• at E14.5 and E15.5

embryo

abnormal placenta vasculature ( J:162690 )

• lack of vessels containing nucleated red blood cells in placenta at E13.5

abnormal vitelline vasculature morphology ( J:162690 )

• reduced vascular network in mutant yolk sac at E13.5

decreased embryo size ( J:162690 )

• at E14.5 and E15.5

thin placenta labyrinth ( J:162690 )

• decrease in the thickness of the labyrinth layer of the placenta at E13.5

cardiovascular system

abnormal blood vessel morphology ( J:162690 )

• fewer blood vessels in the brain, spinal cord and skin at E13.5

abnormal placenta vasculature ( J:162690 )

• lack of vessels containing nucleated red blood cells in placenta at E13.5

abnormal vitelline vasculature morphology ( J:162690 )

• reduced vascular network in mutant yolk sac at E13.5

dilated vasculature ( J:162690 )

• dilation of vessels in the brain, spinal cord and skin at E12.5

hemorrhage ( J:162690 )

• perivascular hemorrhages at E13.5

increased vascular permeability ( J:162690 )

• increased permeability after Ad-Cre infection of ECs in vitro

homeostasis/metabolism

edema ( J:162690 )

• at E13.5

Genotype
MGI:5502187

cn27

• Allelic Composition: Cxcr4^tm1Tng/Cxcr4^tm2Tng; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

cardiovascular system

poor arterial differentiation ( J:195048 )

abnormal skin vasculature morphology ( J:195048 )

• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice

• however, vascular density is normal

abnormal developmental vascular remodeling ( J:195048 )

• disorganized branching patterns in developing limb skin

abnormal vascular smooth muscle morphology ( J:195048 )

• reduced smooth muscle cell coverage of small diameter branched vessels

• however, coverage of large diameter veins is normal

nervous system

nervous system phenotype ( J:195048 )

N • mice exhibit normal innervation accompanied by migrating Schwann cells

integument

abnormal skin vasculature morphology ( J:195048 )

• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice

• however, vascular density is normal

muscle

abnormal vascular smooth muscle morphology ( J:195048 )

• reduced smooth muscle cell coverage of small diameter branched vessels

• however, coverage of large diameter veins is normal

Genotype
MGI:4442226

cn28

• Allelic Composition: Tg(CAG-Bgeo,-tsA58T)T26Ichi/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

mortality/aging

premature death ( J:159206 )

• animals are born and grow normally, but suddenly die between 6 and 12 weeks after birth

Genotype
MGI:3583921

cn29

• Allelic Composition: Ptk2^tm1.1Guan/Ptk2^tm1.2Guan; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * C57BL/6J

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:99637 )

• mutant embryos are progressively lost starting at E13.5 with only 3% of pups at birth having the conditional null genotype

cardiovascular system

abnormal vascular endothelial cell morphology ( J:99637 )

• endothelial cells lining small capillaries have pyknotic and karyorrhetic changes and many are rounded, detached, and sloughing off into the lumen

• apoptotic and necrotic endothelial cells are seen

abnormal capillary morphology ( J:99637 )

• many capillaries with abnormal endothelial cells are collapsed

abnormal placenta vasculature ( J:99637 )

• arterial canals and canal branches lack fetal red blood cells and some of the vessels appear collapsed; however the heart appears normal

abnormal vascular branching morphogenesis ( J:99637 )

• at E13.5, the vascular network in the head is reduced and no clear outlines of viscera or axial skeleton with PECAM-1 staining

abnormal vitelline vasculature morphology ( J:99637 )

• fewer branched vessels and a marked decrease in sprouting angiogenesis are seen in the yolk sac

hemorrhage ( J:99637 )

• at E13.5, multifocal, scattered, and variably sized hemorrhages are seen and at E14.5 these are large and superficial

• at E13.5, the thickened dermis also has numerous perivascular hemorrhages

embryo

abnormal placenta vasculature ( J:99637 )

• arterial canals and canal branches lack fetal red blood cells and some of the vessels appear collapsed; however the heart appears normal

abnormal vitelline vasculature morphology ( J:99637 )

• fewer branched vessels and a marked decrease in sprouting angiogenesis are seen in the yolk sac

embryonic growth retardation ( J:99637 )

• seen in about 5% of embryos at E10.5

decreased embryo size ( J:99637 )

abnormal amnion morphology ( J:99637 )

• thickening of the amnion as a result of edema

• prominent amniotic blood vessels are not seen

thin placenta labyrinth ( J:99637 )

• the thickness of the placental labyrinth is reduced

homeostasis/metabolism

edema ( J:99637 )

• present in the membranes of the amnion at E13.5 and superficially at E14.5

growth/size/body

embryonic growth retardation ( J:99637 )

• seen in about 5% of embryos at E10.5

decreased embryo size ( J:99637 )

integument

thick dermal layer ( J:99637 )

• at E13.5, thickening and expansion of the dermis with loosely arranged mesenchymal cells mixed with acellular pale esosinophilic material

Genotype
MGI:5553270

cn30

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm3Jhjh; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N

hematopoietic system

hematopoietic system phenotype ( J:206925 )

N • mice exhibit normal blood cell parameters and colony-forming progenitors in the bone marrow

Genotype
MGI:4820572

cn31

• Allelic Composition: Ptk2^tm2.1Guan/Ptk2^tm1.1Guan; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:162690 )

• fewer mutant embryos are recovered than Mendelian ratios starting at embryonic day (E)14.5; none are alive at birth

• no perivascular hemorrhages, normal vessels containing nucleated red blood cells, normal vascularization in placenta at E13.5

cardiovascular system

abnormal blood vessel morphology ( J:162690 )

• decreased number of vessels in the brain, spinal cord and skin at E13.5

dilated vasculature ( J:162690 )

• dilated vessels in the brain, spinal cord and skin at E12.5

increased vascular permeability ( J:162690 )

• increased permeability after recombinant adenoviruses encoding Cre infection of endothelial cells in vitro

cellular

increased apoptosis ( J:162690 )

• a slight increase in apoptosis in the liver at E13.5

Genotype
MGI:5471939

cn32

• Allelic Composition: Dlk1^tm1.1Jvs/Dlk1⁺; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N

mortality/aging

mortality/aging ( J:194130 )

N • mice exhibit normal survival

growth/size/body

growth/size/body region phenotype ( J:194130 )

N • mice exhibit normal growth

Genotype
MGI:3697608

cn33

• Allelic Composition: Acvr1^tm1Vk/Acvr1^tm1.1Vk; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:103532 )

• only 10% of the expected 25% of mutants are recovered at E14.5

cardiovascular system

abnormal vascular endothelial cell differentiation ( J:103532 )

• endothelial cells (atrioventricular canal tissues) fail to transdifferentiate in vitro

abnormal cardiac epithelial to mesenchymal transition ( J:103532 )

• endothelial cells fail to populate the mesenchyme of the atrioventricular cushions

abnormal heart morphology ( J:103532 )

• at E14.5, surviving embryos show a range of cardiac defects

abnormal atrioventricular cushion morphology ( J:103532 )

• atrioventricular cushions are of variable shape and degree of fusion with one another, or with other septal structures

decreased atrioventricular cushion size ( J:103532 )

• endocardial cushions are smaller at E10; reduction in mesenchymal cell number is particularly evident in the superior cushion

• atrioventricular cushions are of variable size

abnormal atrioventricular valve development ( J:103532 )

• 11 of 17 E14.5 embryos have defective atrioventricular valve development

• outgrowth and formation of atrioventricular leaflets is variable

atrial septal defect ( J:103532 )

• the primary atrial foramen is still patent at E14.5 in some embryos, allowing blood to shunt between right and the left atria

abnormal atrioventricular septum morphology ( J:103532 )

• 11 of 17 E14.5 embryos have defective atrioventricular septation

ventricular septal defect ( J:103532 )

• 15 of 17 E14.5 embryos have a ventricular septal defect of varying severity, where the secondary ventricular foramen has not closed

cardiovascular shunt ( J:103532 )

• the primary atrial foramen is still patent at E14.5 in some embryos, allowing blood to shunt between right and the left atria

cellular

abnormal vascular endothelial cell differentiation ( J:103532 )

• endothelial cells (atrioventricular canal tissues) fail to transdifferentiate in vitro

Genotype
MGI:3717920

cn34

• Allelic Composition: Sox17^tm1Sjm/Sox17^tm2Sjm; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6 * C57BL/Ka

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:123050 )

• expected numbers of homozygotes are found at E12.5, but complete lethality is observed by E13.5

embryo

embryonic growth retardation ( J:123050 )

• at E12.5, mutants are growth retarded

abnormal embryonic hematopoiesis ( J:123050 )

• no hematopoiesis is visible in the yolk sac or embryo at E12.5

growth/size/body

embryonic growth retardation ( J:123050 )

• at E12.5, mutants are growth retarded

hematopoietic system

abnormal embryonic hematopoiesis ( J:123050 )

• no hematopoiesis is visible in the yolk sac or embryo at E12.5

Genotype
MGI:3699178

cn35

• Allelic Composition: Gba1^tm1Clk/Gba1^tm1.1Clk; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6J

immune system

abnormal macrophage morphology ( J:117763 )

• lipid-laden macrophages are found in liver and spleen beginning at 16 weeks of age; these have tissue-paper like cytoplasmic inclusions (Gaucher cells)

• macrophages with organized glucocerebroside storage material enclosed in membrane bound lysosomal extensions are observed in affected spleens at 26 weeks

abnormal spleen morphology ( J:117763 )

• rafts of lipid engorged macrophages are observed

• by 26 weeks, spleens are visibly mottled with a fatty and cobbled surface appearance

increased spleen weight ( J:117763 )

• overt in 2/3 of animals by 26 weeks of age; weight is as much as 6 times control value

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:117763 )

• glucocerebrosidase activity level is reduced to 50% of controls in all tissues; activity is variable in peripheral white cells, ranging from <3% to 30%

liver/biliary system

abnormal liver morphology ( J:117763 )

• by 26 weeks, liver contains Gaucher cells, with some rafting

hematopoietic system

abnormal macrophage morphology ( J:117763 )

• lipid-laden macrophages are found in liver and spleen beginning at 16 weeks of age; these have tissue-paper like cytoplasmic inclusions (Gaucher cells)

• macrophages with organized glucocerebroside storage material enclosed in membrane bound lysosomal extensions are observed in affected spleens at 26 weeks

abnormal spleen morphology ( J:117763 )

• by 26 weeks, spleens are visibly mottled with a fatty and cobbled surface appearance

• rafts of lipid engorged macrophages are observed

increased spleen weight ( J:117763 )

• overt in 2/3 of animals by 26 weeks of age; weight is as much as 6 times control value

skeleton

abnormal bone marrow morphology ( J:117763 )

• small numbers of Gaucher cells can be found

growth/size/body

increased spleen weight ( J:117763 )

• overt in 2/3 of animals by 26 weeks of age; weight is as much as 6 times control value

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Gaucher's disease type I		DOID:0110957	OMIM:230800	J:117763

Genotype
MGI:3845662

cn36

• Allelic Composition: Vcam1^tm2Flv/Vcam1^tm3Flv; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S1/Sv * C3H * C57BL/6

growth/size/body

decreased body weight ( J:107447 )

• weigh about 10% less than controls

spleen hyperplasia ( J:107447 )

• modest but significant increase in spleen cellularity

immune system

spleen hyperplasia ( J:107447 )

• modest but significant increase in spleen cellularity

decreased B cell number ( J:68147 )

• decrease in the number of IgD+ B cells in the bone marrow

decreased immature B cell number ( J:68147 )

• decrease in the number of IgD^loIgM^hi immature B cells in the bone marrow

decreased CD4-positive, alpha-beta T cell number ( J:68147 )

• the fraction of naive CD4+ T cells is decreased in the bone marrow

decreased CD8-positive, alpha-beta T cell number ( J:68147 )

• decrease in the number of CD8+ T cells in the bone marrow

increased leukocyte cell number ( J:68147 , J:107447 )

• mild (J:68147)

• increased WBC number with a higher proportion of B220+ cells and a lower proportion of Mac-1+ cells (J:107447)

increased immature B cell number ( J:68147 )

• increase in the number of B220+IgD^loIgM^hi immature B cells in the periphery

abnormal splenic cell ratio ( J:107447 )

• increase in the number of progenitor cells

abnormal lymphocyte physiology ( J:68147 )

• however, migration to the spleen and lymph nodes is similar to controls

• impaired lymphocyte short term migration to the bone marrow

impaired B cell migration ( J:68147 )

• impaired short term migration of IgD+ cells to the bone marrow

abnormal CD4-positive, alpha-beta T cell physiology ( J:68147 )

• impaired short term migration of CD4+ cells to the bone marrow

abnormal CD8-positive, alpha-beta T cell physiology ( J:68147 )

• impaired short term migration of CD8+ cells to the bone marrow

cellular

impaired B cell migration ( J:68147 )

• impaired short term migration of IgD+ cells to the bone marrow

hematopoietic system

spleen hyperplasia ( J:107447 )

• modest but significant increase in spleen cellularity

abnormal blood cell morphology/development ( J:107447 , J:123142 )

• increase in the number of progenitor cells in the peripheral blood in young and old mice (J:107447)

• the number of colony forming unit cultures in the peripheral blood is increased compared to controls (J:123142)

abnormal bone marrow cell morphology/development ( J:107447 , J:123142 )

• treatment with anti-VLA4 antibody fails to mobilize progenitor cells from the bone marrow to the peripheral blood (J:107447)

• in response to granulocyte colony stimulating factor (G-CSF) more mobilized progenitors are found in the peripheral blood and fewer progenitors are found in the spleen compared to controls (J:107447)

• after G-CSF treatment or G-CSF plus Flt3 ligand treatment total progenitor cell numbers from all hematopoietic organs are decreased compared to controls (J:107447)

• treatment with anti-alpha4 antibody fails to mobilize progenitor cells from the bone marrow to the peripheral blood (J:123142)

• following irradiation, homing of wild-type donor cells to the bone marrow is impaired (J:123142)

decreased bone marrow cell number ( J:68147 , J:107447 )

• decrease in the number of IgD^loIgM^hi immature B cells, IgD+ B cells and CD8+ T cells in the bone marrow (J:68147)

• the fraction of naive CD4+ T cells is decreased (J:68147)

• however, no decrease in the number of pro-B cells is detected in the bone marrow and the total number of bone marrow cells is similar to controls (J:68147)

• in both young (9 - 14 weeks of age) and old (over 40 weeks of age) mice (J:107447)

• moderate decrease in progenitor content in young but not in old mice (J:107447)

decreased B cell number ( J:68147 )

• decrease in the number of IgD+ B cells in the bone marrow

decreased immature B cell number ( J:68147 )

• decrease in the number of IgD^loIgM^hi immature B cells in the bone marrow

decreased CD4-positive, alpha-beta T cell number ( J:68147 )

• the fraction of naive CD4+ T cells is decreased in the bone marrow

decreased CD8-positive, alpha-beta T cell number ( J:68147 )

• decrease in the number of CD8+ T cells in the bone marrow

increased leukocyte cell number ( J:68147 , J:107447 )

• mild (J:68147)

• increased WBC number with a higher proportion of B220+ cells and a lower proportion of Mac-1+ cells (J:107447)

increased immature B cell number ( J:68147 )

• increase in the number of B220+IgD^loIgM^hi immature B cells in the periphery

abnormal splenic cell ratio ( J:107447 )

• increase in the number of progenitor cells

abnormal lymphocyte physiology ( J:68147 )

• impaired lymphocyte short term migration to the bone marrow

• however, migration to the spleen and lymph nodes is similar to controls

impaired B cell migration ( J:68147 )

• impaired short term migration of IgD+ cells to the bone marrow

abnormal CD4-positive, alpha-beta T cell physiology ( J:68147 )

• impaired short term migration of CD4+ cells to the bone marrow

abnormal CD8-positive, alpha-beta T cell physiology ( J:68147 )

• impaired short term migration of CD8+ cells to the bone marrow

Genotype
MGI:4887353

cn37

• Allelic Composition: Ddah1^tm1Yjch/Ddah1^tm1Yjch; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S1/Sv * C57BL/6J

homeostasis/metabolism

abnormal amino acid level ( J:168130 )

• increased levels of asymmetric dimethyl arginine in lung, liver, and kidney

• symmetric dimethyl arginine is elevated by about 60% only in lung

abnormal circulating amino acid level ( J:168130 )

• increased levels of asymmetric dimethyl arginine in plasma

abnormal nitric oxide homeostasis ( J:168130 )

• acetylcholine induced stimulation of NO production in isolated aortic rings is attenuated

cardiovascular system

cardiovascular system phenotype ( J:168130 )

N • cardiac structure and function is normal

increased systemic vascular resistance ( J:168130 )

increased left ventricle systolic pressure ( J:168130 )

increased systemic arterial blood pressure ( J:168130 )

increased mean systemic arterial blood pressure ( J:168130 )

increased systemic arterial systolic blood pressure ( J:168130 )

• including aortic systolic pressure

abnormal vascular smooth muscle physiology ( J:168130 )

• isolated aortic ring relaxation is reduced

muscle

abnormal vascular smooth muscle physiology ( J:168130 )

• isolated aortic ring relaxation is reduced

Genotype
MGI:5696327

cn38

• Allelic Composition: Gipc1^tm1.1Mhsi/Gipc1^tm1.1Mhsi; Tg(Tek-cre)12Flv/?
• Genetic Background: involves: 129S1/SvImJ * 129S4/SvJaeSor * C3H * C57BL/6

cardiovascular system

abnormal systemic artery morphology ( J:221554 )

• less arterial branching and fewer collateral arteries in heart and kidney

• significant decrease in smaller arteries

• fewer arteriolar linkages in the spinotrapezius and a more dendritic arterial tree

• narrower input arterioles

coronary artery aneurysm ( J:221554 )

• aneurismal dilations in distal coronary arteries

abnormal blood circulation ( J:221554 )

• impaired recovery of blood flow after hind limb ischemia

Genotype
MGI:5444445

cn39

• Allelic Composition: Nostrin^tm1Oess/Nostrin^tm1Oess; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S2/SvPas * C3H * C57BL/6

cardiovascular system

abnormal vascular endothelial cell migration ( J:188414 )

• vascular endothelial cells in the retina exhibit reduced migration with reduced number of filopodia at the leading edge of the expanding vascular plexus compared to in wild-type mice

decreased vascular endothelial cell proliferation ( J:188414 )

• vascular endothelial cells in the retina exhibit reduced proliferation

cellular

abnormal vascular endothelial cell migration ( J:188414 )

• vascular endothelial cells in the retina exhibit reduced migration with reduced number of filopodia at the leading edge of the expanding vascular plexus compared to in wild-type mice

decreased vascular endothelial cell proliferation ( J:188414 )

• vascular endothelial cells in the retina exhibit reduced proliferation

Genotype
MGI:3822161

cn40

• Allelic Composition: Mapk1^tm1Melo/Mapk1⁺; Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S2/SvPas * C3H * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:142212 )

• all mice died by E14.5

cardiovascular system

increased atrioventricular cushion size ( J:142212 )

double outlet right ventricle ( J:142212 )

• the frequency of double outlet right ventricles is greater than in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice

ventricular septal defect ( J:142212 )

• the frequency of ventricular septal defects is greater than in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice

abnormal cardiovascular system physiology ( J:142212 )

• proliferation of endothelial, mesenchymal, and cardiomyocyte cells is increased while apoptosis rates are decreased compared to in wild-type

liver/biliary system

hepatic necrosis ( J:142212 )

homeostasis/metabolism

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

integument

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

growth/size/body

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

Genotype
MGI:5706726

cn41

• Allelic Composition: Mir92-1^tm1Sdim/Mir92-1^tm1Sdim; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S2/SvPas * C3H * C57BL/6J

mortality/aging

mortality/aging ( J:218943 )

N • mice are observed in Mendelian ratios

Genotype
MGI:5473521

cn42

• Allelic Composition: Plvap^tm1.1Rvst/Plvap^tm1.1Rvst; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6

mortality/aging

lethality, incomplete penetrance ( J:191046 )

• Background Sensitivity: display 100% lethality by P2 on a congenic C57BL/6 background unlike mice on a mixed background where about 20-30% of mice survive to 6-7 months of age

cardiovascular system

abnormal capillary morphology ( J:191046 )

• lack diaphragms in endothelial fenestrae, transendothelial channels, and caveolae in pancreas, intestine, kidney, lung and adrenals

increased vascular permeability ( J:191046 )

• leakage of Evans Blue dye is dramatically increased in organs with fenestrated endothelial cells

• leakage of Evans Blue dye is highest in the intestine

homeostasis/metabolism

abnormal circulating lipid level ( J:191046 )

decreased circulating HDL cholesterol level ( J:191046 )

• significantly decreased at 4 weeks of age and does not vary much with time

increased circulating cholesterol level ( J:191046 )

• moderate increase at 4 weeks of age that does not vary much with time

increased circulating triglyceride level ( J:191046 )

• plasma levels are increased 30- to 100-fold from 4 to 8 weeks of age

decreased circulating total protein level ( J:191046 )

ascites ( J:191046 )

• fluid contains albumin and beta globins at similar levels to blood plasma but sharply reduced alpha fractions

growth/size/body

postnatal growth retardation ( J:191046 )

distended abdomen ( J:191046 )

• due to accumulation of ascites

adipose tissue

decreased white adipose tissue amount ( J:191046 )

endocrine/exocrine glands

small pancreas ( J:191046 )

Genotype
MGI:3716393

cn43

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6

embryo

embryo phenotype ( J:119477 )

N • mutants show normal vascularization of the yolk sac and placental labyrinth

Genotype
MGI:5490533

cn44

• Allelic Composition: Adgrf5^tm1.1Bstc/Adgrf5^tm1.2Bstc; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6J

respiratory system

respiratory system phenotype ( J:196943 )

N • mice exhibit normal surfactant homeostasis in the lung

Genotype
MGI:4836837

cn45

• Allelic Composition: Tfpi^tm1.1Rdsi/Tfpi^tm1.1Rdsi; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * BALB/cJ * C3H * C57BL/6

homeostasis/metabolism

abnormal circulating protein level ( J:164530 )

• decreased tissue factor pathway inhibitor protein level and activity

increased susceptibility to induced thrombosis ( J:164530 )

• in a FeCl3 arterial injury model, carotid arteries become occluded faster than in control mice

Genotype
MGI:4414850

cn46

• Allelic Composition: Ate1^tm2.1Akas/Ate1^tm2.1Akas; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C3H * C57BL/6 * CD-1

Ate1^tm2.1Akas/Ate1^tm2.1Akas Tg(Tek-cre)12Flv/0 mice have delayed development and die at early post-implantation stages

reproductive system

reduced fertility ( J:155427 )

• homozygous mice mated to homozygous mice produce embryos that die prior to E8.5

• homozygous mice mated to homozygous mice produce embryos that when extracted at E2.5 and cultured develop slower than wild-type mice

• however, female mice exhibit normal angiogenic-related processes during pregnancy and both female and male mice exhibit expected litter survival when mated to wild-type mice or Ate1^tm1Akas homozygotes

decreased litter size ( J:155427 )

• 2 pups per litter comapred to 7 pups per litter for Ate1^tm2.1Akas Tg(Tek-cre)12Flv heterozygotes

Genotype
MGI:4360980

cn47

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Wnk1)Clhu}/Gt(ROSA)26Sor⁺; Wnk1^{Gt(OST38262)Lex}/Wnk1^{Gt(OST38262)Lex}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S5/SvEvBrd * C3H * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:152906 )

• all but one, died within 1 day of birth

• however, the early lethality seen in single Wnk1 homozygotes does not occur

cardiovascular system

cardiovascular system phenotype ( J:152906 )

N • unlike single Wnk1 homozygotes, heart morphology is grossly normal at E15.5

embryo

abnormal embryo development ( J:152906 )

• the incidence of abnormal embryos is increased compared to controls indicating only a partial rescue

Genotype
MGI:3663893

cn48

• Allelic Composition: Metap2^tm1.1Ccr/Metap2^tm1.1Ccr; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:111701 )

• survive past early gestation period but die by E10.5

growth/size/body

decreased embryo size ( J:111701 )

• appear smaller at E9.5

embryo

embryonic growth arrest ( J:111701 )

• develop to midsomite stage (E8.5) but become arrested and necrotic at E9.5

decreased embryo size ( J:111701 )

• appear smaller at E9.5

disorganized embryonic tissue ( J:111701 )

• embryos appear disorganized at E9.5

embryo tissue necrosis ( J:111701 )

• embryos become necrotic at E9.5

cardiovascular system

abnormal blood vessel morphology ( J:111701 )

decreased vascular endothelial cell number ( J:111701 )

• embryos contain fewer PECAM-positive endothelial cells

abnormal intersomitic vessel morphology ( J:111701 )

• intersomitic vessels are either poorly developed or fail to be distinguished

abnormal vascular development ( J:111701 )

• blood vessels, such as the dorsal aorta, intersomitic vessels, and small capillary plexus are either poorly developed or fail to be distinguished, indicating arrest of vascular development

abnormal dorsal aorta morphology ( J:111701 )

• dorsal aorta is either poorly developed or fails to be distinguished

Genotype
MGI:3840254

cn49

• Allelic Composition: Ptpn11^tm6Bgn/Ptpn11⁺; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6

mortality/aging

embryonic lethality ( J:147154 )

cardiovascular system

thin myocardium ( J:147154 )

• seen at E13.5

increased atrioventricular cushion size ( J:147154 )

• seen at E11.5 and E13.5

double outlet right ventricle ( J:147154 )

ventricular septal defect ( J:147154 )

muscle

thin myocardium ( J:147154 )

• seen at E13.5

Genotype
MGI:3848804

cn50

• Allelic Composition: Zfx^tm1.1Reiz/Y; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6

hematopoietic system

abnormal common lymphocyte progenitor cell morphology ( J:149654 )

♂

decreased mature B cell number ( J:149654 )

♂

decreased T cell number ( J:149654 )

♂ • mature T cells are decreased compared to in wild-type mice

decreased hematopoietic stem cell number ( J:149654 )

♂ • mice exhibit a reduction in hematopoietic stem cells and specifically self-renewing long-term hematopoietic stem cells compared to in wild-type mice

abnormal hematopoietic system physiology ( J:149654 )

♂ • maintenance of adult hematopoietic cells is abolished compared to in wild-type mice

immune system

decreased mature B cell number ( J:149654 )

♂

decreased T cell number ( J:149654 )

♂ • mature T cells are decreased compared to in wild-type mice

Genotype
MGI:5306357

cn51

• Allelic Composition: Kitl^tm1.1Sjm/Kitl^tm2.1Sjm; Lepr^tm2(cre)Rck/Lepr⁺; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/Ka * SJL

hematopoietic system

spleen hyperplasia ( J:180431 )

decreased bone marrow cell number ( J:180431 )

decreased hematopoietic cell number ( J:180431 )

• in the bone marrow

immune system

spleen hyperplasia ( J:180431 )

growth/size/body

spleen hyperplasia ( J:180431 )

Genotype
MGI:4950916

cn52

• Allelic Composition: Ppp2ca^tm1.1Nju/Ppp2ca^tm1.1Nju; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:171578 )

• a further loss of mice is seen between E12.5 and E14.5

• however, some mice survive to adulthood

embryonic lethality during organogenesis, incomplete penetrance ( J:171578 )

• the expected number of mice are found at E10.5 but fewer than expected are found at E12.5

hematopoietic system

abnormal erythropoiesis ( J:171578 )

• fetal livers contain very few erythrocytes but numbers of other hematopoietic lineage cells are similar to controls at E12.5

• severe impairment in the differentiation of proerythroblasts into erythroblasts in the fetal liver at E14.5

• total numbers of BFU-E and CFU-E are dramatically lower in fetal livers compared to controls

• however, embryonic erythropoiesis is similar to controls

anemia ( J:171578 )

• severe in embryos

• however, surviving adults have normal steady-state hematocrit

decreased fetal derived definitive erythrocyte cell number ( J:171578 )

• dramatic reduction in the number of erythrocytes in the fetal liver at E14.5

increased hematopoietic stem cell number ( J:171578 )

• increase in the number of LSK cells in the fetal liver at E14.5

abnormal erythrocyte physiology ( J:171578 )

• cultured erythroid cells are more sensitive to apoptotic stimulation compared to control cells

liver/biliary system

abnormal liver morphology ( J:171578 )

• enlarged fetal liver cells and reduced total liver cellularity at E12.5 and E14.5

• livers contain very few hematopoietic cells unlike in controls at E12.5

pale liver ( J:171578 )

• at E12.5

cardiovascular system

cardiovascular system phenotype ( J:171578 )

N • despite recombination in endothelial cells, no obvious vascular defects are detected

integument

pallor ( J:171578 )

• at E12.5

Genotype
MGI:5464105

cn53

• Allelic Composition: Tab1^tm1Mis/Tab1^tm1Mis; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S7/SvEvBrd * C3H * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:191285 )

• mice are born at a normal Mendelian ratio and did not exhibit any gross abnormalities and normal blood vessel structure

Genotype
MGI:4946112

cn54

• Allelic Composition: Agtr1a^tm1Uky/Agtr1a^tm1Uky; Ldlr^tm1Her/Ldlr^tm1Her; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S7/SvEvBrd * C3H * C57BL/6 * C57BL/6N

cardiovascular system

abnormal aorta elastic fiber morphology ( J:170230 )

• angiotensin II-treated mice fed a high-fat diet exhibit decreased elastin breaks compared with similarly treated Ldlr^tm1Her homozygotes

decreased aorta wall thickness ( J:170230 )

• angiotensin II-treated mice fed a high-fat diet exhibit decreased medial thickness compared with similarly treated Ldlr^tm1Her homozygotes

abnormal ascending aorta morphology ( J:170230 )

• angiotensin II-treated mice fed a high-fat diet exhibit less ascending aorta lengthening compared with similarly treated Ldlr^tm1Her homozygotes

decreased susceptibility to induced aneurysm formation ( J:170230 )

• angiotensin II-treated mice fed a high-fat diet exhibit less ascending aorta ulcers compared with similarly treated Ldlr^tm1Her homozygotes

Genotype
MGI:2176622

cn55

• Allelic Composition: Efnb2^tm1And/Efnb2^tm2And; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:74909 )

• mutant embryos die by E11

cardiovascular system

abnormal intersomitic vessel morphology ( J:74909 )

• embryos exhibit an arrest in intersomitic vessel angiogenesis at the primary plexus stage; the vessels appear fused dorsally with little or no branching

abnormal vascular development ( J:74909 )

• vasculature is disorganized and less developed

abnormal angiogenesis ( J:74909 )

• E9.5 mutants exhibit a failure of anterior cardinal vein assembly

• the capillary bed of the head appears dilated and arrested at the primary plexus stage

• embryos exhibit an arrest in intersomitic vessel angiogenesis at the primary plexus stage; the vessels appear fused dorsally with little or no branching

abnormal developmental vascular remodeling ( J:74909 )

• E9.5 mutants exhibit a failure of anterior cardinal vein assembly and remodeling

abnormal vitelline vasculature morphology ( J:74909 )

• yolk sac is a homogeneous capillary bed at E9.5, indicating arrest of artery and vein development at the primary plexus stage

absent myocardial trabeculae ( J:74909 )

• little or no myocardial trabecular extensions by E9

abnormal heart looping ( J:74909 )

• heart looping defects

enlarged heart ( J:74909 )

• hearts are swollen at E9.5

embryo

abnormal vitelline vasculature morphology ( J:74909 )

• yolk sac is a homogeneous capillary bed at E9.5, indicating arrest of artery and vein development at the primary plexus stage

embryonic growth arrest ( J:74909 )

• embryos are developmentally less advanced at E9.5

decreased embryo size ( J:74909 )

• evident at E10

growth/size/body

enlarged heart ( J:74909 )

• hearts are swollen at E9.5

decreased embryo size ( J:74909 )

• evident at E10

muscle

absent myocardial trabeculae ( J:74909 )

• little or no myocardial trabecular extensions by E9

Genotype
MGI:4881715

cn56

• Allelic Composition: Ackr3^tm1Twb/Ackr3^tm1.1Twb; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S/SvEv * BALB/cJ * C3H * C57BL/6

cardiovascular system

abnormal myocardial fiber morphology ( J:167833 )

• cellular disarray and enlarged intercellular spaces at 6 months of age

increased myocardial fiber size ( J:167833 )

• at 6 months of age

myocardial fiber disarray ( J:167833 )

cardiac hypertrophy ( J:167833 )

• marked hypertrophy at 6 months of age with much thicker ventricle walls but no change in the size of the ventricular cavity

heart left ventricle hypertrophy ( J:167833 )

• the wall is about 1.4 fold thicker than controls

thick aortic valve ( J:167833 )

• at 6 months of age

• increase in thickness is greater in the aortic valve compared to the pulmonary valve

thick pulmonary valve ( J:167833 )

• at 6 months of age

• increase in thickness is greater in the aortic valve compared to the pulmonary valve

cardiac fibrosis ( J:167833 )

• at 6 months of age

growth/size/body

cardiac hypertrophy ( J:167833 )

• marked hypertrophy at 6 months of age with much thicker ventricle walls but no change in the size of the ventricular cavity

heart left ventricle hypertrophy ( J:167833 )

• the wall is about 1.4 fold thicker than controls

muscle

abnormal myocardial fiber morphology ( J:167833 )

• cellular disarray and enlarged intercellular spaces at 6 months of age

increased myocardial fiber size ( J:167833 )

• at 6 months of age

myocardial fiber disarray ( J:167833 )

heart left ventricle hypertrophy ( J:167833 )

• the wall is about 1.4 fold thicker than controls

Genotype
MGI:5514138

cn57

• Allelic Composition: Mir21a^tm1.1Zqy/Mir21a^tm1.1Zqy; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S/SvEv * C3H * C57BL/6 * SJL

Decrease in elastin and collagen content in Mir21a^tm1.1Zqy/Mir21a^tm1.1Zqy Tg(Tek-cre)12Flv/0 aorta

cardiovascular system

abnormal aorta collagen fibril morphology ( J:199907 )

• decreased collagen

decreased aorta elastin content ( J:199907 )

abnormal thoracic aorta morphology ( J:199907 )

• increased opening angle, decreased inner diameter, increased wall thickness/inner diameter ratio

• decreased elastin and collagen content and increased aortic stiffness

decreased mean systemic arterial blood pressure ( J:199907 )

decreased systemic arterial diastolic blood pressure ( J:199907 )

abnormal blood vessel physiology ( J:199907 )

• decreased norepinephrine-induced maximal tension in aortic strips

• increased aortic stiffness and decreased compliance of the aorta

decreased vasodilation ( J:199907 )

• decreased sensitivity to acetylcholine induced relaxation

muscle

decreased vasodilation ( J:199907 )

• decreased sensitivity to acetylcholine induced relaxation

Genotype
MGI:4840270

cn58

• Allelic Composition: Adgra2^tm1Cjku/Adgra2^tm2Cjku; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129/Sv * C3H * C57BL/6

cardiovascular system

abnormal blood vessel morphology ( J:166127 )

• basally localized glomeruloid malformations in hemorrhagic areas of the CNS

internal hemorrhage ( J:166127 )

• stated to be identical to the phenotype seen in mice homozygous for Gpr124^tm1Cjku

• forebrain hemorrhage

Genotype
MGI:3822163

cn59

• Allelic Composition: Mapk3^tm1Gpg/Mapk3⁺; Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129/Sv * C3H * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:142212 )

• all mice died by E14.5

cardiovascular system

increased atrioventricular cushion size ( J:142212 )

• endocardial cushion volume is increased compared to in wild-type mice but not as severely as in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice

liver/biliary system

hepatic necrosis ( J:142212 )

homeostasis/metabolism

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

integument

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

growth/size/body

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

Genotype
MGI:3822162

cn60

• Allelic Composition: Mapk3^tm1Gpg/Mapk3^tm1Gpg; Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129/Sv * C3H * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:142212 )

• all mice died by E14.5

• however, Mendelian ratios of embryos are present at E13.5

cardiovascular system

cardiovascular system phenotype ( J:142212 )

N • mice exhibit normal endocardial cushion size and rates of proliferation and apoptosis of endothelial and mesenchymal cushion cells

liver/biliary system

hepatic necrosis ( J:142212 )

homeostasis/metabolism

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

integument

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

growth/size/body

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

Genotype
MGI:5563907

cn61

• Allelic Composition: Smo^tm2Amc/Smo^tm2Amc; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129X1/SvJ * C3H * C57BL/6

cardiovascular system

cardiovascular system phenotype ( J:204743 )

N • cardiopulmonary development is not disrupted

Genotype
MGI:5285614

cn62

• Allelic Composition: H2-Ab1^b-tm1Koni/H2-Ab1^b-tm1.1Koni; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129X1/SvJ * C3H * C57BL/6 * C57BL/6J

immune system

immune system phenotype ( J:131774 )

N • T regulatory cells exhibit division in response to IL2

N • CD4+CD25+ exhibit effective suppressive activity

increased CD4-positive, alpha-beta T cell number ( J:131774 )

• 1.5- to 2-fold in CD4+CD8- but not CD8-CD4+CD25+

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:131774 )

• CD4+CD25+ fopx3^high T regulatory cells exhibit reduced CD25 expression compared with control cells

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:131774 )

• 2-fold

abnormal T cell activation ( J:131774 )

• mice exhibit a reduced number of preactivated CD4 T cells and CD4+CD25+ cells compared with wild-type mice

decreased level of surface class II molecules ( J:131774 )

• in splenic hemopoietic cells (B cells, CD8a- dendritic cells, and CD8a+ dendritic cells) and Langerhans cells

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:131774 )

• 1.5- to 2-fold in CD4+CD8- but not CD8-CD4+CD25+

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:131774 )

• CD4+CD25+ fopx3^high T regulatory cells exhibit reduced CD25 expression compared with control cells

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:131774 )

• 2-fold

abnormal T cell activation ( J:131774 )

• mice exhibit a reduced number of preactivated CD4 T cells and CD4+CD25+ cells compared with wild-type mice

Genotype
MGI:5285615

cn63

• Allelic Composition: H2-Ab1^b-tm1.1Koni/H2-Ab1^b-tm1.1Koni; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129X1/SvJ * C3H * C57BL/6 * C57BL/6J

mortality/aging

preweaning lethality, incomplete penetrance ( J:131774 )

• fewer than expected mice are produced

Genotype
MGI:4843921

cn64

• Allelic Composition: Smo^tm2Amc/Smo^tm2.1Amc; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6

cardiovascular system

cardiovascular system phenotype ( J:135134 )

N • mice exhibit normal outflow tract development

Genotype
MGI:5306355

cn65

• Allelic Composition: Kitl^tm2.1Sjm/Kitl^tm2.2Sjm; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: BALB/cJ * C3H * C57BL/6 * C57BL/Ka * SJL

hematopoietic system

hematopoietic system phenotype ( J:180431 )

N • mice exhibit normal blood cell counts and bone marrow and spleen cellularity

decreased hematopoietic cell number ( J:180431 )

• to a greater extent than in Kitl^tm2.2Sjm heterozygotes in the bone marrow

• 1.7-2.1-fold in the liver of newborn mice

• 2-fold in the bone marrow of 1 month old mice

• 2.7-5.2-fold in the bone marrow of 8 week old mice

abnormal bone marrow cell physiology ( J:180431 )

• bone marrow cells from tamoxifen-treated mice used to repopulate irradiated mice exhibit reduced bone marrow-derived cell production (total, myeloid, T cell, and B cell)

Genotype
MGI:6385861

cn66

• Allelic Composition: Hspd1^{tm1c(EUCOMM)Hmgu}/Hspd1^{tm1c(EUCOMM)Hmgu}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: Black Swiss * C3H * C57BL/6 * C57BL/6N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:282096 )

• embryos are seen at the expected Mendelian ratio at E10.5 but all embryos between E11.5 and E13.5 are dead and absorbed

cardiovascular system

abnormal blood vessel morphology ( J:282096 )

• some vessels exhibit reduced diameters in the head, trunk, and yolk sac at E10.5 but not E9.5

• however, marker analysis shows that endothelial cell differentiation and early development of the yolk sac vascular system appear normal

embryo

embryonic growth retardation ( J:282096 )

• E10.5, but not E9.5, embryos are growth retarded

growth/size/body

embryonic growth retardation ( J:282096 )

• E10.5, but not E9.5, embryos are growth retarded

hematopoietic system

anemia ( J:282096 )

• E10.5 embryos develop severe anemia and are pale

abnormal blood cell morphology ( J:282096 )

• E10.5 embryos exhibit an abnormally low number of blood cells in embryos or yolk sacs

decreased erythrocyte cell number ( J:282096 )

• the numbers of yolk sac erythrocytes are reduced at E9

• however, blood distribution in yolk sacs is similar to controls at E8.5 and the numbers of yolk sac erythrocytes are normal at E8.5

abnormal erythrocyte physiology ( J:282096 )

• cell apoptosis of yolk sac erythrocytes is increased at E9 but not E8.5

• treatment with cyclosporine A decreases erythrocyte cell apoptosis

• mitochondrial membrane potentials of Ter119+ erythrocytes from E8.5 yolk sacs are slightly, but significantly, lower than in controls

Genotype
MGI:3765432

cn67

• Allelic Composition: Klf2^tm1Mlkn/Klf2^tm1Mlkn; Tg(Tek-cre)12Flv/?
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:127228 )

• embryos are all dead by E14.5

cardiovascular system

thin myocardium ( J:127228 )

• by E12.5, the myocardium of is only 1-2 cell layers thick compared to a thickness of 5 cell layers or more in littermate controls

detached epicardium ( J:127228 )

• by E12.5, the myocardium has pulled away from the epicardium

pericardial effusion ( J:127228 )

• by E12.5, large effusions are apparent around the embryonic heart

increased cardiac output ( J:127228 )

• in E11.5 embryos, cardiac outputs are nearly 3 fold higher than in littermate controls

increased cardiac stroke volume ( J:127228 )

• in E11.5 embryos, left ventricular stroke volume is 2.5 fold higher than in controls

• no evidence of valvular regurgitation is detected, indicating that excess flow is in the outward direction

decreased systemic vascular resistance ( J:127228 )

• maternal administration of a smooth muscle tone agonist rescues half of E14.5 embryos from lethality related to cardiac failure

absent heartbeat ( J:127228 )

• at E12.5, 25% of embryos lack a heartbeat with the remaining embryos having a slower heartbeat (86 bpm vs 128 bpm)

• by E14.5 all embryos have lost their heartbeat

embryo

pale yolk sac ( J:127228 )

• at E12.5, some yolk sacs are poorly perfused while others are devoid of blood

hematopoietic system

anemia ( J:127228 )

• mice have normal amounts of erthyrocytes and do not display other signs of anemia

homeostasis/metabolism

pericardial effusion ( J:127228 )

• by E12.5, large effusions are apparent around the embryonic heart

muscle

thin myocardium ( J:127228 )

• by E12.5, the myocardium of is only 1-2 cell layers thick compared to a thickness of 5 cell layers or more in littermate controls

Genotype
MGI:3839597

cn68

• Allelic Composition: Smad7^tm1Shou/Smad7^tm1Shou; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:145777 )

• fewer than expected mice survive pre-weaning

cardiovascular system

abnormal cardiovascular development ( J:145777 )

abnormal heart development ( J:145777 )

• developing heart trabecular myocardium and endocardium proliferation is increased compared to in wild-type mice

abnormal atrioventricular cushion morphology ( J:145777 )

• at E14.5, apoptosis in the atrioventricular cushion is increased compared to in wild-type mice

transposition of great arteries ( J:145777 )

abnormal heart ventricle morphology ( J:145777 )

• mice exhibit ventricular non-compaction unlike in wild-type mice

abnormal trabecula carnea morphology ( J:145777 )

• the right ventricle trabecular area is increased compared to in wild-type mice

ventricular septal defect ( J:145777 )

decreased heart right ventricle wall thickness ( J:145777 )

• thin right ventricle wall

abnormal blood circulation ( J:145777 )

• mice exhibit an increase in systolic ventricular chamber volume compared to in wild-type mice

decreased cardiac muscle contractility ( J:145777 )

• mice exhibit decreased fractional shortening and ejection fraction compared to wild-type mice

prolonged RR interval ( J:145777 )

• the R-R interval is increased compared to in wild-type mice

irregular heartbeat ( J:145777 )

• mice exhibit arrhythmias

abnormal QRS complex ( J:145777 )

• although the QRS duration is normal, the QRS complex exhibits morphological abnormalities compared to in wild-type mice

growth/size/body

decreased body size ( J:145777 )

• neonatally

muscle

abnormal trabecula carnea morphology ( J:145777 )

• the right ventricle trabecular area is increased compared to in wild-type mice

decreased cardiac muscle contractility ( J:145777 )

• mice exhibit decreased fractional shortening and ejection fraction compared to wild-type mice

homeostasis/metabolism

skin edema ( J:145777 )

• at E14.5 and E16.5

integument

skin edema ( J:145777 )

• at E14.5 and E16.5

pallor ( J:145777 )

• mice are pale at E14.5, E16.5, and after birth

Genotype
MGI:6361094

cn69

• Allelic Composition: Nus1^tm1Wcsa/Nus1^tm1Wcsa; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:230506 )

• lethality between E10.5 and E11.5

growth/size/body

decreased embryo size ( J:230506 )

• embryos are smaller at E10.5 but not at E8.5 or E9.5

embryo

abnormal placenta vasculature ( J:230506 )

• placentas show dilated embryonic vessels and decreased numbers of embryonic vessels

abnormal vitelline vasculature morphology ( J:230506 )

• yolk sacs are poorly organized with dilated primitive capillaries and have no large vitelline vessels

abnormal embryo morphology ( J:230506 )

• E10.5 embryos are paler than controls

decreased embryo size ( J:230506 )

• embryos are smaller at E10.5 but not at E8.5 or E9.5

thin placenta labyrinth ( J:230506 )

• the labyrinthine layers of the placenta are thinner

excessive folding of visceral yolk sac ( J:230506 )

• yolk sacs are dimpled and wrinkled at E9.5

abnormal visceral yolk sac physiology ( J:230506 )

• yolk sacs at E9.5 show 39% reductions in endothelial cell proliferation

• yolk sacs at E9.5 show increased apoptosis of endothelial cells

cardiovascular system

abnormal placenta vasculature ( J:230506 )

• placentas show dilated embryonic vessels and decreased numbers of embryonic vessels

abnormal vitelline vasculature morphology ( J:230506 )

• yolk sacs are poorly organized with dilated primitive capillaries and have no large vitelline vessels

abnormal vascular endothelial cell physiology ( J:230506 )

• hypoglycosylation of endothelial proteins including VEGFR2

Genotype
MGI:5634707

cn70

• Allelic Composition: Il1r1^tm1Quan/Il1r1^tm1Quan; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6

hematopoietic system

abnormal microglial cell activation ( J:219864 )

• microglia are activated (deramified) throughout the brain prenchyma following IL1beta injection

immune system

abnormal microglial cell activation ( J:219864 )

• microglia are activated (deramified) throughout the brain prenchyma following IL1beta injection

abnormal inflammatory response ( J:219864 )

• intracerebroventricular IL1beta administration results in leukocyte infiltration (CD45+ cell trafficking) to the brain parenchyma 12 hours after injection

nervous system

abnormal microglial cell activation ( J:219864 )

• microglia are activated (deramified) throughout the brain prenchyma following IL1beta injection

Genotype
MGI:4360979

cn71

• Allelic Composition: Wnk1^tm1Clhu/Wnk1^tm1Clhu; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:152906 )

• all die before E13.5

cardiovascular system

abnormal dorsal aorta morphology ( J:152906 )

• at E10.5, dorsal aortae are collapsed

abnormal brain vasculature morphology ( J:152906 )

• at E10.5 the density of vessels in the head is reduced

abnormal vascular branching morphogenesis ( J:152906 )

• reduced branching angiogenesis

abnormal cardinal vein morphology ( J:152906 )

• at E10.5 the cardinal veins are collapsed

abnormal vitelline vasculature morphology ( J:152906 )

• at E10.5, lack visible large vessels

abnormal myocardial trabeculae morphology ( J:152906 )

• reduced at E10.5

thin myocardium ( J:152906 )

• at E10.5

heart hypoplasia ( J:152906 )

• at E10.5 all 4 chambers are formed but are hypoplastic

pericardial edema ( J:152906 )

• at E10.5

embryo

abnormal vitelline vasculature morphology ( J:152906 )

• at E10.5, lack visible large vessels

decreased embryo size ( J:152906 )

• at E10.5

abnormal vitelline vascular remodeling ( J:152906 )

• at E10.5 the primitive plexus has failed to remodel

homeostasis/metabolism

pericardial edema ( J:152906 )

• at E10.5

growth/size/body

decreased embryo size ( J:152906 )

• at E10.5

muscle

abnormal myocardial trabeculae morphology ( J:152906 )

• reduced at E10.5

thin myocardium ( J:152906 )

• at E10.5

nervous system

abnormal brain vasculature morphology ( J:152906 )

• at E10.5 the density of vessels in the head is reduced

Genotype
MGI:5488609

cn72

• Allelic Composition: Cxcl12^tm1.1Sjm/Cxcl12^tm1.1Sjm; Tg(Tek-cre)12Flv/?
• Genetic Background: involves: C3H * C57BL/6

hematopoietic system

decreased hematopoietic stem cell number ( J:194748 )

abnormal bone marrow cell physiology ( J:194748 )

• reduced effectiveness in donor cell reconstitution

Genotype
MGI:4867008

cn73

• Allelic Composition: Jag1^tm2Grid/Jag1^tm2Grid; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:166769 )

• die at approximately E10.5

cardiovascular system

abnormal vascular smooth muscle morphology ( J:166769 )

• non-cell autonomous defects in vascular smooth muscle cell differentiation

pericardial edema ( J:166769 )

hemorrhage ( J:166769 )

embryo

abnormal vitelline vascular remodeling ( J:166769 )

• fail to remodel the primary vascular plexus of the yolk sac to form large blood vessels

homeostasis/metabolism

pericardial edema ( J:166769 )

muscle

abnormal vascular smooth muscle morphology ( J:166769 )

• non-cell autonomous defects in vascular smooth muscle cell differentiation

Genotype
MGI:4950281

cn74

• Allelic Composition: Ccl2^tm1.1Pame/Ccl2^tm1.1Pame; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6

immune system

abnormal leukocyte migration ( J:171379 )

• LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice

• mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice

increased susceptibility to bacterial infection ( J:171379 )

• mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice

cellular

abnormal leukocyte migration ( J:171379 )

• LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice

• mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice

hematopoietic system

abnormal leukocyte migration ( J:171379 )

• LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice

• mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice

Genotype
MGI:3723119

cn75

• Allelic Composition: Ackr3^tm1Fma/Ackr3^tm1Fma; Tg(Tek-cre)12Flv/?
• Genetic Background: involves: C3H * C57BL/6

cardiovascular system

abnormal aortic valve cusp morphology ( J:124878 )

• 25% of neonates exhibit aortic valve tricuspids with thick leaflets

• 4.2% of neonates exhibit aortic valve bicuspids with thick leaflets

• 8.3% of neonates have an aortic valve bicuspid or unicuspid with an overgrown and obstructed leaflet

bicuspid aortic valve ( J:124878 )

• 4.2% of neonates exhibit aortic valve bicuspids with thick leaflets

• 8.3% of neonates have an aortic valve bicuspid or unicuspid with an overgrown and obstructed leaflet

thick aortic valve cusps ( J:124878 )

• 25% of neonates exhibit aortic valve tricuspids with thick leaflets

• 4.2% of neonates exhibit aortic valve bicuspids with thick leaflets

unicuspid aortic valve ( J:124878 )

• some neonates have an aortic valve unicuspid with an overgrown and obstructed leaflet

abnormal pulmonary valve cusp morphology ( J:124878 )

• 17% of neonates exhibit pulmonary valve tricuspids with thick leaflets

• 4.2% of neonates have a pulmonary valve bicuspid or unicuspid with an overgrown and obstructed leaflet

bicuspid pulmonary valve ( J:124878 )

• 4.2% of neonates have a pulmonary valve bicuspid or unicuspid with an overgrown and obstructed leaflet

thick pulmonary valve cusps ( J:124878 )

• 17% of neonates exhibit pulmonary valve tricuspids with thick leaflets

unicuspid pulmonary valve ( J:124878 )

• some neonates have a pulmonary valve unicuspid with an overgrown and obstructed leaflet

dilated heart right ventricle ( J:124878 )

• 26% of neonates have dilated right ventricles

Genotype
MGI:4822129

cn76

• Allelic Composition: Bmal1^tm2Bra/Bmal1^tm2Bra; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6J

behavior/neurological

decreased locomotor activity ( J:155089 )

• in the rest and active phases

cardiovascular system

increased heart rate ( J:155089 )

• in the rest and active phases

decreased mean systemic arterial blood pressure ( J:155089 )

• within the active phase

homeostasis/metabolism

abnormal protein level ( J:155089 )

• mice fail to exhibit circadian alterations in total plasma tissue plasminogen activator (tPA) levels unlike similarly treated wild-type mice

• however, circadian alteration in plasminogen activator inhibitor-1 (PAI-1) levels is normal

abnormal response to injury ( J:155089 )

• time to thrombotic vascular occlusion (TTVO) subsequent to photochemical injury is decreased at zeitgeber time (ZT) 14 unlike in similarly treated wild-type mice

Genotype
MGI:5912009

cn77

• Allelic Composition: Pkn2^{tm1c(KOMP)Wtsi}/Pkn2^{tm1c(KOMP)Wtsi}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6N

normal phenotype

no abnormal phenotype detected ( J:229595 )

• viable with no overt vascular phenotypes

Genotype
MGI:7546786

cn78

• Allelic Composition: Creld1^{tm1c(EUCOMM)Wtsi}/Creld1^{tm1c(EUCOMM)Wtsi}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6N * SJL

normal phenotype

no abnormal phenotype detected ( J:304446 )

• mice are born in Mendelian ratios and survive to adulthood with no gross phenotype; despite a slight reduction in left ventricular diastolic diameter, overall heart development and function are normal

Genotype
MGI:3849427

cn79

• Allelic Composition: Mecom^tm1Miku/Mecom⁺; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * CBA

hematopoietic system

decreased hematopoietic stem cell number ( J:149794 )

• the population of lin^- Kit⁺CD34⁺ found among E14.5 fetal liver cells is somewhat reduced

Genotype
MGI:3849426

cn80

• Allelic Composition: Mecom^tm1Miku/Mecom^tm1Miku; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * CBA

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:149794 )

• lethality occurs between E13.5 and E16.5 for most embryos

• a few mice reach adulthood due to the presence of bone marrow cells that escape cre mediated excision

cardiovascular system

hemorrhage ( J:149794 )

• many E13.5 embryos exhibit hemorrhaging

hematopoietic system

decreased hematopoietic stem cell number ( J:149794 )

• the population of lin^- Kit⁺CD34⁺ found among E14.5 fetal liver cells is severely reduced

• the number of myeloid or mixed CFUs isolated from fetal liver is also diminished

homeostasis/metabolism

skin edema ( J:149794 )

• many E13.5 embryos exhibit subcutaneous edema

integument

skin edema ( J:149794 )

• many E13.5 embryos exhibit subcutaneous edema

Genotype
MGI:3822159

cn81

• Allelic Composition: Tg(CAG-cat,-Ptpn11)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:142212 )

N • mice exhibit normal cardiac morphology

Genotype
MGI:6275068

cn82

• Allelic Composition: Tg(ACTB-EGFP,-Kcnj8*)1Wco/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * FVB/N

cardiovascular system

abnormal blood vessel physiology ( J:134852 )

• mice exhibit impaired coronary function, showing elevated basal coronary perfusion pressure of isolated hearts at a constant flow rate

• mice show elevated release of the vasoconstrictor endothelin-1 in the coronary effluent from hearts

• treatment with the ATP-sensitive K⁺ channel blocker glibenclamide fails to produce a vasoconstrictive response as in controls

• mice pretreated with the endothelin-1 receptor antagonist bosentan show normal coronary perfusion pressure

• mice exhibit normal response to coronary vasospasm induced with ergonovine

growth/size/body

growth/size/body region phenotype ( J:134852 )

N • mice exhibit normal body weight and wet heart weight

mortality/aging

mortality/aging ( J:134852 )

N • mice exhibit a normal lifespan

Genotype
MGI:3822160

cn83

• Allelic Composition: Tg(CAG-cat,-Map2k1*)243Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:142212 )

• though present in Mendelian ratios at E13.5, no mice are present after birth

cardiovascular system

increased atrioventricular cushion size ( J:142212 )

Genotype
MGI:3822157

cn84

• Allelic Composition: Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * FVB/N

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:142212 )

• all mice died by E14.5

embryonic lethality during organogenesis, incomplete penetrance ( J:142212 )

• fewer than expected mice are present at E13.5 and no mice are present after birth

cardiovascular system

conotruncal ridge hyperplasia ( J:142212 )

• outflow tract cushion volume is only increased by 39% compared to in wild-type mice

abnormal atrioventricular cushion morphology ( J:142212 )

• at E13.5, valve primordial has not yet undergone differentiation and extracellular remodeling as in wild-type mice

increased atrioventricular cushion size ( J:142212 )

• cushion volume is increased up to 85% compared to in wild-type mice

double outlet right ventricle ( J:142212 )

• in some mice

ventricular septal defect ( J:142212 )

• in some mice

abnormal cardiovascular system physiology ( J:142212 )

• proliferation of endothelial, mesenchymal, and cardiomyocyte cells is increased compared to in wild-type

• proliferation of cells in the atrioventricular canal cushion endothelial and mesenchymal cell proliferation is increased while apoptosis is decreased compared to in wild-type mice

• however, proliferation of cardiomyocytes in the atrioventricular canal cushion is normal

hemorrhage ( J:142212 )

• at E13.5

ventricular cardiomyopathy ( J:142212 )

• some mice exhibit ventricular noncompaction

embryo

decreased embryo size ( J:142212 )

• at E13.5

growth/size/body

decreased embryo size ( J:142212 )

• at E13.5

nuchal edema ( J:142212 )

• at E13.5

homeostasis/metabolism

edema ( J:142212 )

• at E13.5, mice exhibit nuchal and back edema

nuchal edema ( J:142212 )

• at E13.5

liver/biliary system

small liver ( J:142212 )

• at E13.5

hepatic necrosis ( J:142212 )

muscle

ventricular cardiomyopathy ( J:142212 )

• some mice exhibit ventricular noncompaction

integument

nuchal edema ( J:142212 )

• at E13.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 1		DOID:0060578	OMIM:163950	J:142212

Genotype
MGI:6157438

cn85

• Allelic Composition: Pdia4^{tm1b(EUCOMM)Wtsi}/Pdia4^{tm1b(EUCOMM)Wtsi}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6N

hematopoietic system

hematopoietic system phenotype ( J:244748 )

N • mice exhibit normal platelet counts and size, prothrombin time, partial thromboplastin time, and fibrinogen levels

decreased platelet aggregation ( J:244748 )

homeostasis/metabolism

decreased platelet aggregation ( J:244748 )

increased bleeding time ( J:244748 )

Genotype
MGI:5607596

cn86

• Allelic Composition: Lman1^{tm1c(KOMP)Wtsi}/Lman1^{tm1c(KOMP)Wtsi}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N

homeostasis/metabolism

abnormal blood homeostasis ( J:213133 )

• mice show a reduction in plasma coagulation factor VIII (FVIII) activity levels

• however plasma coagulation factor V (FV) activity is normal

hematopoietic system

abnormal platelet morphology ( J:213133 )

• modest reduction in platelet FV antigen

Genotype
MGI:5824010

cn87

• Allelic Composition: Piezo1^{tm1c(KOMP)Wtsi}/Piezo1^{tm1c(KOMP)Wtsi}; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C57BL/6J * C57BL/6N
• Cell Lines: EPD0500_5_F12

growth/size/body

embryonic growth retardation ( J:217082 )

• embryos exhibit growth retardation at E10.5

embryo

abnormal vitelline vasculature morphology ( J:217082 )

• at E9.5 and E10.5, embryos exhibit disrupted yolk sac vasculature development

embryonic growth retardation ( J:217082 )

• embryos exhibit growth retardation at E10.5

cardiovascular system

abnormal vitelline vasculature morphology ( J:217082 )

• at E9.5 and E10.5, embryos exhibit disrupted yolk sac vasculature development

Genotype
MGI:3042042

cn88

• Allelic Composition: Mapk7^tm1Jdl/Mapk7^tm1Jdl; Tg(Tek-cre)12Flv/0
• Genetic Background: Not Specified

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:89215 )

• fetuses died between E9.5 and E10.5 exhibiting cardiovascular defects

cardiovascular system

abnormal vitelline vasculature morphology ( J:89215 )

• abnormal yolk sac blood vessels, appearing loose and fragile

trabecula carnea hypoplasia ( J:89215 )

• reduced trabeculation in the ventricular chamber

abnormal heart development ( J:89215 )

• impaired myocardium development when compared to controls

abnormal endocardium morphology ( J:89215 )

• impaired endocardium development with the abnormally shaped endothelial cells irregularly aligning with the myocardium

embryo

abnormal vitelline vasculature morphology ( J:89215 )

• abnormal yolk sac blood vessels, appearing loose and fragile

muscle

trabecula carnea hypoplasia ( J:89215 )

• reduced trabeculation in the ventricular chamber

Genotype
MGI:4414849

tg89

• Allelic Composition: Tg(Tek-cre)12Flv/Tg(Tek-cre)12Flv
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

embryonic lethality between somite formation and embryo turning, incomplete penetrance ( J:155427 )

• litters from mice mated to Tg(Tek-cre)12Flv mice produce litters that exhibit 5-10% lethality at E8.5