Phenotypes associated with this allele

• Allele Symbol: Tg(Sp7-tTA,tetO-EGFP/cre)1Amc
• Allele Name: transgene insertion 1, Andrew P McMahon
• Allele ID: MGI:3689350
• Summary: 65 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0 Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N	MGI:5519099
cn2	Trp53^tm1Brn/Trp53^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N	MGI:5519100
cn3	Dicer1^tm1Mmk/Dicer1^tm1Mmk Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * C57BL/6 * CD-1	MGI:4452405
cn4	Rb1^tm3Tyj/Rb1^+ Sox2^tm4.1Skn/Sox2^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * C57BL/6 * CD-1	MGI:7484197
cn5	Rb1^tm3Tyj/Rb1^+ Sox2^tm4.1Skn/Sox2^tm4.1Skn Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * C57BL/6 * CD-1	MGI:7484195
cn6	Rb1^tm3Tyj/Rb1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129 * C57BL/6 * CD-1	MGI:7484192
cn7	Prmt1^tm1c(EUCOMM)Wtsi/Prmt1^+ Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1	MGI:7486124
cn8	Prmt1^tm1a(EUCOMM)Wtsi/Prmt1^tm1a(EUCOMM)Wtsi Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1	MGI:7486120
cn9	Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1	MGI:5521545
cn10	Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:5519094
cn11	Cdkn1b^tm1Jro/Cdkn1b^tm1Jro Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:7484794
cn12	Rb1^tm3Tyj/Rb1^+ Trp53^tm1Brn/Trp53^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:5519097
cn13	Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:5519096
cn14	Rb1^tm3Tyj/Rb1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:5519095
cn15	Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * CD-1	MGI:7482546
cn16	Atrx^tm1Rjg/Atrx^tm1Rjg Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * CD-1	MGI:7482547
cn17	Atrx^tm1Rjg/Y Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * CD-1	MGI:7482548
cn18	Myc^tm2Fwa/Myc^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * CD-1	MGI:7485842
cn19	Myc^tm2Fwa/Myc^tm2Fwa Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * CD-1	MGI:7485843
cn20	Fosl2^tm2Wag/Fosl2^tm2Wag Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:5586500
cn21	Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:5521544
cn22	Runx3^tm1.1Itok/Runx3^tm1.1Itok Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:7485832
cn23	Runx3^tm1Itan/Runx3^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:7485833
cn24	Runx3^tm1Itan/Runx3^tm1Itan Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:7485836
cn25	Rr420^tm1.1Itok/Rr420^tm1.1Itok Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:7486534
cn26	Rr420^em1Itok/Rr420^em1Itok Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:7486536
cn27	Cxcl12^tm1Tng/Cxcl12^tm1.1Link Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * FVB/N	MGI:5468941
cn28	Pkd1^tm3Jzh/Pkd1^tm3Jzh Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?	involves: 129P2/OlaHsd * CD-1	MGI:3811610
cn29	Tnfsf11^tm1.1Caob/Tnfsf11^tm1.1Caob Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S * 129X1/SvJ * C57BL/6 * CD-1	MGI:5297382
cn30	Hif1a^tm3Rsjo/Hif1a^tm3Rsjo Vhl^tm1Jae/Vhl^tm1Jae Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1	MGI:5432006
cn31	Epas1^tm1Mcs/Epas1^tm1Mcs Hif1a^tm3Rsjo/Hif1a^tm3Rsjo Vhl^tm1Jae/Vhl^tm1Jae Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1	MGI:5432005
cn32	Fbn1^tm1.1Itl/Fbn1^tm3Rmz Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J * CD-1	MGI:5439642
cn33	Epas1^tm1Mcs/Epas1^tm1Mcs Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:5432004
cn34	Ctnnb1^tm1Max/Ctnnb1^tm2Kem Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3689415
cn35	Epas1^tm1Mcs/Epas1^tm1Mcs Hif1a^tm3Rsjo/Hif1a^tm3Rsjo Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:5432003
cn36	Gt(ROSA)26Sor^tm4(Wnt7b)Flng/Gt(ROSA)26Sor^+ Rptor^tm1Rueg/Rptor^tm1Rueg Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:5613582
cn37	Gt(ROSA)26Sor^tm4(Wnt7b)Flng/Gt(ROSA)26Sor^+ Rptor^tm1Rueg/Rptor^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:5613583
cn38	Gt(ROSA)26Sor^tm1(Vegfa*)Jhai/Gt(ROSA)26Sor^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * CD-1 * ICR	MGI:4429124
cn39	Epas1^tm1Mcs/Epas1^tm1Mcs Vhl^tm1Jae/Vhl^tm1Jae Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S4/SvJae * 129X1/SvJ * CD-1	MGI:5432007
cn40	Casr^tm1Wch/Casr^tm1Wch Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:5306892
cn41	Rb1^tm3Tyj/Rb1^tm3Tyj Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0 Tg(tetO-RNAi:Trp53)ASlowe/0	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:5521547
cn42	Amer1^tm1.1Nbar/Y Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL	MGI:5086012
cn43	Rb1^tm3Tyj/Rb1^tm3Tyj Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S4/SvJae * C57BL/6J * CD-1	MGI:5519098
cn44	Vhl^tm1Jae/Vhl^tm1Jae Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S4/SvJae * CD-1	MGI:5432002
cn45	Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1	MGI:7281134
cn46	Mbtps1^tm1Jdh/Mbtps1^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1	MGI:7281135
cn47	Smad4^tm2.1Cxd/Smad4^tm2.1Cxd Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6J * CD-1	MGI:5604139
cn48	Smad4^tm2.1Cxd/Smad4^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6J * CD-1	MGI:5604140
cn49	Egln1^tm2Fong/Egln1^tm2Fong Egln2^tm2Fong/Egln2^tm2Fong Egln3^tm2Fong/Egln3^tm2Fong Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6NCr * CD-1	MGI:5432008
cn50	Cthrc1^tm1.1Suna/Cthrc1^tm1.1Suna Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S6/SvEvTac * C57BL/6NTac * CD-1	MGI:5544624
cn51	Smo^tm1Amc/Smo^tm2Amc Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129X1/SvJ * CD-1	MGI:3689417
cn52	Evc2^tm2.1Mis/Evc2^tm2.1Mis Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129X1/SvJ * CD-1	MGI:5698049
cn53	Ctnnb1^tm1Mmt/Ctnnb1^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129X1/SvJ * CD-1	MGI:3689416
cn54	Mmp14^tm1Stjw/Mmp14^tm1Stjw Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: C57BL/6 * CD-1	MGI:5520089
cn55	Sbds^tm1Dats/Sbds^tm1Dats Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: C57BL/6 * CD-1	MGI:4452404
cn56	Nfatc1^tm3Glm/Nfatc1^tm3Glm Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?	involves: C57BL/6 * CD-1	MGI:3831756
cn57	Usp34^em1Qyn/Usp34^em1Qyn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: C57BL/6J * CD-1	MGI:6256537
cn58	Rnf146^tm1.1Rtpl/Rnf146^tm1.1Rtpl Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: C57BL/6J * CD-1	MGI:6150914
cn59	Chd7^em1Kangn/Chd7^em1Kangn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: C57BL/6J * CD-1	MGI:7491815
cn60	Runx3^tm3Yg/Runx3^tm3Yg Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: CD-1	MGI:5689563
cn61	Ctsk^tm1.1Rbar/Ctsk^tm1.1Rbar Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: CD-1	MGI:5492068
cn62	Gt(ROSA)26Sor^tm4(Wnt7b)Flng/Gt(ROSA)26Sor^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: CD-1	MGI:5613581
cx63	Col1a1^tm2(tetO-Fosl2,-DsRed)Wag/Col1a1^+ Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:5586499
cx64	Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0 Tg(tetO-RNAi:Trp53)ASlowe/0	involves: C57BL/6 * CD-1	MGI:5521546
tg65	Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: CD-1	MGI:5604141

Genotype
MGI:5519099

cn1

• Allelic Composition: Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N

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

mortality/aging

premature death ( J:136693 )

• mice die from around 250 to 375 days of age

neoplasm

increased metastatic potential ( J:136693 )

• tumors show metastasis, most frequently to the lung and then the liver

increased osteosarcoma incidence ( J:136693 )

• complete penetrance of osteosarcomas with an average latency of 292 days

skeleton

increased osteosarcoma incidence ( J:136693 )

• complete penetrance of osteosarcomas with an average latency of 292 days

Genotype
MGI:5519100

cn2

• Allelic Composition: Trp53^tm1Brn/Trp53⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N

neoplasm

increased osteosarcoma incidence ( J:136693 )

• low penetrance (8.33%) of osteosarcomas with a long latency of 338 days of age on average

skeleton

increased osteosarcoma incidence ( J:136693 )

• low penetrance (8.33%) of osteosarcomas with a long latency of 338 days of age on average

Genotype
MGI:4452405

cn3

• Allelic Composition: Dicer1^tm1Mmk/Dicer1^tm1Mmk; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1

mortality/aging

decreased tumor-free survival time ( J:158901 )

• mice with tumors die by 4 to 5 weeks of age

• 30% of mice die by 8 weeks of age

craniofacial

increased facial tumor incidence ( J:158901 )

• at 2 to 3 weeks of age, mice develop facial tumors

hematopoietic system

hematopoietic system phenotype ( J:158901 )

N • mice exhibit normal frequency and function of hematopoietic stem cells and progenitors

enlarged spleen ( J:158901 )

• mice with myeloid sarcomas exhibit increased spleen weight with blast cell infiltration unlike in wild-type mice

extramedullary hematopoiesis ( J:158901 )

• in the spleen of some mice

anemia ( J:158901 )

• profound in some mice

impaired hematopoiesis ( J:158901 )

• hematopoietic progenitor cells exhibit increased apoptosis and proliferation compared with wild-type cells

• megakaryocyte-erythroid progenitor cells exhibit increased apoptosis compared to in wild-type mice

• wild-type mice transplanted with transgenic hematopoietic cells exhibit cytopenia and myelodysplastic features

• however, differentiated cells exhibit normal apoptosis

increased bone marrow cell number ( J:158901 )

• in some mice

abnormal megakaryocyte morphology ( J:158901 )

• micro-megakaryocytes with hypolobulated, hyperchromatic nuclei in the bone marrow

abnormal megakaryocyte differentiation ( J:158901 )

• impaired

thrombocytopenia ( J:158901 )

• profound in some mice

giant platelets ( J:158901 )

• giant platelets in the blood

decreased leukocyte cell number ( J:158901 )

• with all subsets of leukocytes exhibiting decreased numbers

decreased B cell number ( J:158901 )

• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice

abnormal myeloid leukocyte morphology ( J:158901 )

• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice

abnormal granulocyte differentiation ( J:158901 )

abnormal neutrophil morphology ( J:158901 )

• hypersegementation

skeleton

abnormal bone structure ( J:158901 )

• texture of mineralized is altered compared to in wild-type mice

• however, trabecular and cortical bone volumes are normal

abnormal bone marrow morphology ( J:158901 )

• bone marrow vascularity is increased compared to in wild-type mice

decreased osteoblast cell number ( J:158901 )

• mildly

abnormal skeleton development ( J:158901 )

• mice exhibit reduced bone marrow stromal osteogenic colony numbers relative to total colony forming numbers compared with wild-type mice

• bone marrow stromal cultured exhibit reduced alkaline phosphatase and calcified matrix deposition compared with wild-type cultures

neoplasm

increased facial tumor incidence ( J:158901 )

• at 2 to 3 weeks of age, mice develop facial tumors

increased hemolymphoid system tumor incidence ( J:158901 )

• at 2 to 3 weeks of age, mice develop myeoblastic tumors

increased leukemia incidence ( J:158901 )

• mice exhibit sporadic acute myelogenous leukemia unlike wild-type mice

increased myeloid sarcoma incidence ( J:158901 )

• mice exhibit sporadic myeloid sarcoma with infiltration behavior unlike wild-type mice

cardiovascular system

abnormal cardiovascular system morphology ( J:158901 )

• bone marrow vascularity is increased compared to in wild-type mice

growth/size/body

increased facial tumor incidence ( J:158901 )

• at 2 to 3 weeks of age, mice develop facial tumors

postnatal growth retardation ( J:158901 )

enlarged spleen ( J:158901 )

• mice with myeloid sarcomas exhibit increased spleen weight with blast cell infiltration unlike in wild-type mice

immune system

enlarged spleen ( J:158901 )

• mice with myeloid sarcomas exhibit increased spleen weight with blast cell infiltration unlike in wild-type mice

decreased leukocyte cell number ( J:158901 )

• with all subsets of leukocytes exhibiting decreased numbers

decreased B cell number ( J:158901 )

• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice

abnormal myeloid leukocyte morphology ( J:158901 )

• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice

abnormal granulocyte differentiation ( J:158901 )

abnormal neutrophil morphology ( J:158901 )

• hypersegementation

cellular

abnormal granulocyte differentiation ( J:158901 )

abnormal megakaryocyte differentiation ( J:158901 )

• impaired

Genotype
MGI:7484197

cn4

• Allelic Composition: Rb1^tm3Tyj/Rb1⁺; Sox2^tm4.1Skn/Sox2⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1

mortality/aging

increased tumor-free survival time ( J:318885 )

• tumor free survival time is increased compared to mutant mice wild-type for Sox2

neoplasm

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

skeleton

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

Genotype
MGI:7484195

cn5

• Allelic Composition: Rb1^tm3Tyj/Rb1⁺; Sox2^tm4.1Skn/Sox2^tm4.1Skn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1

mortality/aging

increased tumor-free survival time ( J:318885 )

• tumor free survival time is increased compared to mutant mice wild-type for Sox2

neoplasm

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

skeleton

decreased osteosarcoma incidence ( J:318885 )

• compared to mutant mice wild-type for Sox2

• tumors are uniformly Sox2 positive

Genotype
MGI:7484192

cn6

• Allelic Composition: Rb1^tm3Tyj/Rb1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1

mortality/aging

decreased tumor-free survival time ( J:318885 )

• decreased tumor free survival time

neoplasm

increased osteosarcoma incidence ( J:318885 )

skeleton

increased osteosarcoma incidence ( J:318885 )

Genotype
MGI:7486124

cn7

• Allelic Composition: Prmt1^{tm1c(EUCOMM)Wtsi}/Prmt1⁺; Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1

mortality/aging

premature death ( J:245660 )

• mice begin to die at ~100 days of age and all die by around 200 days of age, with a median survival similar to that of mutant mice homozygous for the wild-type Prmt1 allele

neoplasm

increased osteosarcoma incidence ( J:245660 )

• microPET/CT imaging suggested an increase in the presence of osteosarcomas at 100 days of age

skeleton

increased osteosarcoma incidence ( J:245660 )

• microPET/CT imaging suggested an increase in the presence of osteosarcomas at 100 days of age

Genotype
MGI:7486120

cn8

• Allelic Composition: Prmt1^{tm1a(EUCOMM)Wtsi}/Prmt1^{tm1a(EUCOMM)Wtsi}; Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1

mortality/aging

increased tumor-free survival time ( J:245660 )

• median tumor-free survival is significantly increased relative to mutant mice that are either homozygotes for the wild-type Prmt1 allele or heterozygotes with one wild-type and one floxed Prmt1 allele

neoplasm

decreased osteosarcoma incidence ( J:245660 )

• microPET/CT imaging suggested a reduction in the presence of osteosarcomas at 100 days of age

• osteosarcoma tumors retain residual PRMT1 protein expression and a nonexcised Prmt1 allele

increased tumor latency ( J:245660 )

• osteosarcoma initiation is delayed relative to mutant mice that are either homozygotes for the wild-type Prmt1 allele or heterozygotes with one wild-type and one floxed Prmt1 allele

skeleton

decreased osteosarcoma incidence ( J:245660 )

• microPET/CT imaging suggested a reduction in the presence of osteosarcomas at 100 days of age

• osteosarcoma tumors retain residual PRMT1 protein expression and a nonexcised Prmt1 allele

Genotype
MGI:5521545

cn9

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1

mortality/aging

premature death ( J:199542 )

• mutants have a median survival of 127 days of age

neoplasm

increased metastatic potential ( J:199542 )

• 20.6% of mice show metastatic dissemination, commonly to the lung and liver

increased hibernoma incidence ( J:199542 )

• seen in one mutant

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 127 days

• 64.7% of tumors are found in the mandible/head, 11.8% of tumors are found on the lower long bones, and 23.5% of tumors are in other axial locations

• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma

skeleton

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 127 days

• 64.7% of tumors are found in the mandible/head, 11.8% of tumors are found on the lower long bones, and 23.5% of tumors are in other axial locations

• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:199542

Genotype
MGI:5519094

cn10

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

skeleton

increased osteosarcoma incidence ( J:136693 , J:318035 )

• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age (J:136693)

• lesions are seen as early as 2 months of age (J:136693)

• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra (J:136693)

• tumors exhibit a histology consistent with human medullary osteosarcoma (J:136693)

• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues (J:136693)

• metastasis is not seen but this may be due to rapid tumor development (J:136693)

• mice maintained on doxycycline from conception until 4 weeks of age (preventing gene inactivation until removal of doxycycline), show delayed osteosarcoma development by about 100 days and these mice present with metastatic osteosarcoma but no head tumors (J:136693)

• mice develop osteosarcomas with 100% penetrance at an average of 154.65 +/- 29.08 days of age (J:318035)

• anatomic distribution of tumors includes the head and jaw (42.9%), limbs (38.8%), trunk (10.2%) and spine and sacrum (8.2%) (J:318035)

mortality/aging

premature death ( J:136693 , J:318035 )

• mice begin to die around 95 days of age and all die by 161 days of age (J:136693)

• mice develop invasive, metastatic osteosarcomas and die within 20-35 weeks of age (J:318035)

growth/size/body

postnatal growth retardation ( J:136693 )

• slight growth delay that resolves with age

neoplasm

increased metastatic potential ( J:318035 )

• mice develop metastatic tumor nodules in the lung

increased tumor incidence ( J:136693 )

• about 20% of mice develop adipogenic tumors which occur on the outer chest or abdomen

increased osteosarcoma incidence ( J:136693 , J:318035 )

• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age (J:136693)

• lesions are seen as early as 2 months of age (J:136693)

• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra (J:136693)

• tumors exhibit a histology consistent with human medullary osteosarcoma (J:136693)

• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues (J:136693)

• metastasis is not seen but this may be due to rapid tumor development (J:136693)

• mice maintained on doxycycline from conception until 4 weeks of age (preventing gene inactivation until removal of doxycycline), show delayed osteosarcoma development by about 100 days and these mice present with metastatic osteosarcoma but no head tumors (J:136693)

• mice develop osteosarcomas with 100% penetrance at an average of 154.65 +/- 29.08 days of age (J:318035)

• anatomic distribution of tumors includes the head and jaw (42.9%), limbs (38.8%), trunk (10.2%) and spine and sacrum (8.2%) (J:318035)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:136693 , J:318035

Genotype
MGI:7484794

cn11

• Allelic Composition: Cdkn1b^tm1Jro/Cdkn1b^tm1Jro; Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

mortality/aging

increased tumor-free survival time ( J:318035 )

• overall survival is significantly longer than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, regardless of whether tumors are located in the jaw or limbs

neoplasm

abnormal tumor pathology ( J:318035 )

• osteosarcoma tumors exhibit a marked increase in mutant p27^T187A levels while tumor lysates show elevated CDKN1B (p27) protein levels with similar SKP2 expression relative to tumors from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

• treatment of early passage tumor cells with CHX (a protein synthesis inhibitor) and MG132 (a proteasome inhibitor) showed enhanced stability of the mutant p27^T187A protein, with no significant change in Cdkn1b (p27) mRNA levels

• TUNEL and cleaved caspase-3 immunostaining showed increased apoptosis, while flow cytometry using annexin V/7-AAD staining showed a significant increase in the early apoptotic population

• primary osteosarcoma tumor cells exhibit less sphere-forming capacity and show reduced stem-like properties (such as ALDH activity) and lower stem-cell frequency and self-renewal ability than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

decreased tumor growth/size ( J:318035 )

• both limb and jaw osteosarcoma tumors are significantly smaller than those from age-matched mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, indicating delayed tumor progression

• in vivo, tumor growth rate is significantly slower than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

• in vitro, primary osteosarcoma cells grown in monolayer cultures proliferate significantly less than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

increased osteosarcoma incidence ( J:318035 )

• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age

• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)

skeleton

increased osteosarcoma incidence ( J:318035 )

• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age

• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)

growth/size/body

growth/size/body region phenotype ( J:318035 )

N • mice show no evidence of delayed or stunted growth

reproductive system

reproductive system phenotype ( J:318035 )

N • mice are fertile

Genotype
MGI:5519097

cn12

• Allelic Composition: Rb1^tm3Tyj/Rb1⁺; Trp53^tm1Brn/Trp53⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

mortality/aging

premature death ( J:136693 )

• about 70% survival at 400 days of age, with some mice starting to die around 150 days of age

neoplasm

increased metastatic potential ( J:136693 )

• tumors show metastasis, most frequently to the lung and then the liver

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes

skeleton

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes

Genotype
MGI:5519096

cn13

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

mortality/aging

premature death ( J:136693 )

• mice start to die from around 125 days of age, although about 20% survive to 400 days of age

neoplasm

increased metastatic potential ( J:136693 )

• tumors show metastasis, most frequently to the lung and then the liver

increased osteosarcoma incidence ( J:136693 )

• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age

skeleton

increased osteosarcoma incidence ( J:136693 )

• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age

Genotype
MGI:5519095

cn14

• Allelic Composition: Rb1^tm3Tyj/Rb1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

mortality/aging

premature death ( J:136693 )

• die from around 125 to 260 days of age

neoplasm

increased metastatic potential ( J:136693 )

• tumors show metastasis, most frequently to the lung and then the liver

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age

skeleton

increased osteosarcoma incidence ( J:136693 )

• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:136693

Genotype
MGI:7482546

cn15

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * CD-1

neoplasm

increased osteosarcoma incidence ( J:329449 )

• show completely penetrant osteosarcoma formation between 4 and 8 months of age

skeleton

increased osteosarcoma incidence ( J:329449 )

• show completely penetrant osteosarcoma formation between 4 and 8 months of age

Genotype
MGI:7482547

cn16

• Allelic Composition: Atrx^tm1Rjg/Atrx^tm1Rjg; Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * CD-1

neoplasm

increased osteosarcoma incidence ( J:329449 )

♀ • tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx

decreased tumor latency ( J:329449 )

♀ • increase in the rate of osteosarcoma initiation compared to mutant mice wild-type for Atrx

skeleton

increased osteosarcoma incidence ( J:329449 )

♀ • tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx

Genotype
MGI:7482548

cn17

• Allelic Composition: Atrx^tm1Rjg/Y; Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * CD-1

neoplasm

increased osteosarcoma incidence ( J:329449 )

♂ • tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx

decreased tumor latency ( J:329449 )

♂ • increase in the rate of osteosarcoma initiation compared to mutant mice wild-type for Atrx

skeleton

increased osteosarcoma incidence ( J:329449 )

♂ • tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx

Genotype
MGI:7485842

cn18

• Allelic Composition: Myc^tm2Fwa/Myc⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * CD-1

neoplasm

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Myc

mortality/aging

increased tumor-free survival time ( J:319454 )

• survival time is increased compared to mutant mice wild-type for Myc

skeleton

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Myc

Genotype
MGI:7485843

cn19

• Allelic Composition: Myc^tm2Fwa/Myc^tm2Fwa; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * CD-1

mortality/aging

premature death ( J:319454 )

• fie before onset of osteosarcoma

Genotype
MGI:5586500

cn20

• Allelic Composition: Fosl2^tm2Wag/Fosl2^tm2Wag; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

skeleton

abnormal osteoblast physiology ( J:211215 )

• fewer mineralized nodules produced from primary osteoblasts under osteogenic conditions

abnormal osteoclast morphology ( J:211215 )

• increased osteoclast surface

decreased bone volume ( J:211215 )

abnormal osteoblast morphology ( J:211215 )

• decreased osteoblast surface

decreased bone trabecula number ( J:211215 )

decreased trabecular bone thickness ( J:211215 )

decreased bone ossification ( J:211215 )

• decreased bone formation

cellular

abnormal osteoblast physiology ( J:211215 )

• fewer mineralized nodules produced from primary osteoblasts under osteogenic conditions

homeostasis/metabolism

decreased circulating glucose level ( J:211215 )

• in mice fed a high fat diet

• however, levels are normal in mice fed a normal diet

decreased circulating osteocalcin level ( J:211215 )

impaired glucose tolerance ( J:211215 )

• in mice fed a normal diet and high fat diet

insulin resistance ( J:211215 )

• in mice fed a high fat diet

• however, mice fed a normal diet exhibit insulin tolerance

growth/size/body

increased body weight ( J:211215 )

• under normal diet and high fat diet

adipose tissue

adipose tissue phenotype ( J:211215 )

N • mice exhibit normal adipocyte number and size

increased gonadal fat pad weight ( J:211215 )

• under normal diet and high fat diet

hematopoietic system

abnormal osteoclast morphology ( J:211215 )

• increased osteoclast surface

immune system

abnormal osteoclast morphology ( J:211215 )

• increased osteoclast surface

Genotype
MGI:5521544

cn21

• Allelic Composition: Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

skeleton

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 226.5 days

• 25% of tumors are found on the mandible/head, 50% of tumors are found on the lower long bones, and 25% of tumors are in other axial locations

• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma

mortality/aging

premature death ( J:199542 )

• mutants have a median survival of 226.5 days of age

decreased tumor-free survival time ( J:319454 )

neoplasm

increased metastatic potential ( J:199542 )

• 50% of mice show metastatic dissemination, commonly to the lung and liver

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 226.5 days

• 25% of tumors are found on the mandible/head, 50% of tumors are found on the lower long bones, and 25% of tumors are in other axial locations

• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:199542

Genotype
MGI:7485832

cn22

• Allelic Composition: Runx3^tm1.1Itok/Runx3^tm1.1Itok; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

neoplasm

decreased osteosarcoma incidence ( J:319454 )

• incidence is decreased compared to mutant mice wild-type for Runx3

mortality/aging

increased tumor-free survival time ( J:319454 )

• increased lifespan compared to mutant mice wild-type for Runx3

skeleton

decreased osteosarcoma incidence ( J:319454 )

• incidence is decreased compared to mutant mice wild-type for Runx3

Genotype
MGI:7485833

cn23

• Allelic Composition: Runx3^tm1Itan/Runx3⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

neoplasm

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Runx3

mortality/aging

increased tumor-free survival time ( J:319454 )

• increased lifespan compared to mutant mice wild-type for Runx3

skeleton

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Runx3

Genotype
MGI:7485836

cn24

• Allelic Composition: Runx3^tm1Itan/Runx3^tm1Itan; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

mortality/aging

premature death ( J:319454 )

• many die before osteosarcoma formation

Genotype
MGI:7486534

cn25

• Allelic Composition: Rr420^tm1.1Itok/Rr420^tm1.1Itok; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

mortality/aging

increased tumor-free survival time ( J:319454 )

• survival time is increased compared to mutant mice wild-type for Rr420

neoplasm

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Rr420

• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3^tm1.1Itok

skeleton

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Rr420

• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3^tm1.1Itok

Genotype
MGI:7486536

cn26

• Allelic Composition: Rr420^em1Itok/Rr420^em1Itok; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

mortality/aging

increased tumor-free survival time ( J:319454 )

• survival time is increased compared to mutant mice wild-type for Rr420

neoplasm

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Rr420

• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3^tm1.1Itok

skeleton

decreased osteosarcoma incidence ( J:319454 )

• decreased incidence compared to mutant mice wild-type for Rr420

• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3^tm1.1Itok

Genotype
MGI:5468941

cn27

• Allelic Composition: Cxcl12^tm1Tng/Cxcl12^tm1.1Link; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * FVB/N

hematopoietic system

abnormal blood cell morphology/development ( J:193594 )

• the numbers of colony-forming cells and KSL cells are increased in the blood and spleen, demonstrating constitutive HPC mobilization, compared with control mice

decreased pre-pro B cell number ( J:193594 )

decreased bone marrow cell number ( J:193594 )

decreased B cell number ( J:193594 )

• in the bone marrow

decreased hematopoietic stem cell number ( J:193594 )

• modest decrease in the absolute number

abnormal hematopoietic stem cell physiology ( J:193594 )

• increased cycling of more mature KSL progenitors in the blood

• however, hematopoietic stem cell cycling is normal

immune system

decreased pre-pro B cell number ( J:193594 )

decreased B cell number ( J:193594 )

• in the bone marrow

Genotype
MGI:3811610

cn28

• Allelic Composition: Pkd1^tm3Jzh/Pkd1^tm3Jzh; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?
• Genetic Background: involves: 129P2/OlaHsd * CD-1

skeleton

delayed intramembranous bone ossification ( J:139970 )

• mice display a delay in intramembranous ossification

• however, no growth defects of the craniofacial bones are found

Genotype
MGI:5297382

cn29

• Allelic Composition: Tnfsf11^tm1.1Caob/Tnfsf11^tm1.1Caob; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S * 129X1/SvJ * C57BL/6 * CD-1

skeleton

skeleton phenotype ( J:177558 )

N • mice treated with doxycycline until 4 months of age exhibit normal cancellous architecture at 6 months

failure of tooth eruption ( J:177558 )

• in all mice

• however, exposure to doxycycline restores tooth eruption

increased bone mineral density ( J:177558 )

• at 5 weeks of age

increased trabecular bone volume ( J:177558 )

• at 5 weeks of age

abnormal cartilage morphology ( J:177558 )

• mice exhibit unresorbed cartilage unlike wild-type mice

increased long bone epiphyseal plate size ( J:177558 )

• widened growth plate in the femur

craniofacial

failure of tooth eruption ( J:177558 )

• in all mice

• however, exposure to doxycycline restores tooth eruption

growth/size/body

failure of tooth eruption ( J:177558 )

• in all mice

• however, exposure to doxycycline restores tooth eruption

Genotype
MGI:5432006

cn30

• Allelic Composition: Hif1a^tm3Rsjo/Hif1a^tm3Rsjo; Vhl^tm1Jae/Vhl^tm1Jae; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1

hematopoietic system

increased hematocrit ( J:186085 )

homeostasis/metabolism

increased circulating erythropoietin level ( J:186085 )

Genotype
MGI:5432005

cn31

• Allelic Composition: Epas1^tm1Mcs/Epas1^tm1Mcs; Hif1a^tm3Rsjo/Hif1a^tm3Rsjo; Vhl^tm1Jae/Vhl^tm1Jae; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1

skeleton

decreased trabecular bone volume ( J:186085 )

decreased bone trabecula number ( J:186085 )

hematopoietic system

hematopoietic system phenotype ( J:186085 )

N • mice exhibit normal frequencies of KLS cells (hematopoietic stem cells and multipotential progenitors) numbers of red blood cells and lymphocytes and hematocrit

homeostasis/metabolism

decreased circulating erythropoietin level ( J:186085 )

Genotype
MGI:5439642

cn32

• Allelic Composition: Fbn1^tm1.1Itl/Fbn1^tm3Rmz; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J * CD-1

skeleton

decreased bone mineral density ( J:187484 )

decreased bone volume ( J:187484 )

abnormal trabecular bone morphology ( J:187484 )

• increased trabecular space

abnormal bone trabecula morphology ( J:187484 )

• worse trabeculae morphology compared with Fbn1^tm2Rmz homozygotes

decreased bone trabecula number ( J:187484 )

decreased trabecular bone thickness ( J:187484 )

decreased bone mass ( J:187484 )

Genotype
MGI:5432004

cn33

• Allelic Composition: Epas1^tm1Mcs/Epas1^tm1Mcs; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

hematopoietic system

decreased erythroid progenitor cell number ( J:186085 )

• decreased frequency of CD71+/Ter119+ cells in the bone marrow

Genotype
MGI:3689415

cn34

• Allelic Composition: Ctnnb1^tm1Max/Ctnnb1^tm2Kem; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

limbs/digits/tail

abnormal limb development ( J:114494 )

• at E16.5, clear zones of hypertrophy are visible in limbs compared to controls

skeleton

arrested osteoblast differentiation ( J:114494 )

• in mutant tibia, no Oc+ osteoblasts are detected, indicating failure of osteoblast progression to terminal osteoblasts

abnormal cartilage morphology ( J:114494 )

• hypertrophic chondrocytes line the periosteal region in addition to the normal growth plate

abnormal bone ossification ( J:114494 )

• membranous bone cranial ossification centers are absent at E18.5

• ossification in mutant periosteum of the tibia is absent

abnormal bone mineralization ( J:114494 )

• at E18.5, mutant limbs show absence of mineralized bone matrix compared to wild-type embryos and remaining mineralization is associated with hypertrophic chondrocytes; there appears to be complete loss of bone deposition

cellular

arrested osteoblast differentiation ( J:114494 )

• in mutant tibia, no Oc+ osteoblasts are detected, indicating failure of osteoblast progression to terminal osteoblasts

Genotype
MGI:5432003

cn35

• Allelic Composition: Epas1^tm1Mcs/Epas1^tm1Mcs; Hif1a^tm3Rsjo/Hif1a^tm3Rsjo; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

hematopoietic system

hematopoietic system phenotype ( J:186085 )

N • mice exhibit normal hematopoietic stem cell frequency

decreased erythroid progenitor cell number ( J:186085 )

• decreased frequency of CD71+/Ter119+ cells in the bone marrow

skeleton

decreased trabecular bone volume ( J:186085 )

Genotype
MGI:5613582

cn36

• Allelic Composition: Gt(ROSA)26Sor^{tm4(Wnt7b)Flng}/Gt(ROSA)26Sor⁺; Rptor^tm1Rueg/Rptor^tm1Rueg; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

skeleton

abnormal bone structure ( J:208766 )

• when cre expression is suppressed by doxycycline treatment until 1 month of age then stopped, 3 weeks later bone mass is reduced compared to mutant mice with one wild-type Rptor allele

abnormal bone marrow cavity morphology ( J:208766 )

• when cre expression is suppressed by doxycycline treatment until 1 month of age then stopped, 3 weeks later bone marrow cavity is larger than in mutant mice with one wild-type Rptor allele but still smaller than in controls not over expressing Wnt7b

increased osteoblast cell number ( J:208766 )

• when cre expression is suppressed by doxycycline treatment until 1 month of age then stopped, 3 weeks later osteoblast number is increased

• however, unlike in mice with one wild-type Rptor osteoblast hyperactivity is reduced

Genotype
MGI:5613583

cn37

• Allelic Composition: Gt(ROSA)26Sor^{tm4(Wnt7b)Flng}/Gt(ROSA)26Sor⁺; Rptor^tm1Rueg/Rptor⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

skeleton

abnormal bone marrow cavity morphology ( J:208766 )

• when cre expression is suppressed by doxycycline treatment until 1 month of age the marrow cavity is decreased

increased bone mass ( J:208766 )

• when cre expression is suppressed by doxycycline treatment until 1 month of age mice show very high bone mass 3 weeks after stopping doxycycline treatment

Genotype
MGI:4429124

cn38

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Vegfa*)Jhai}/Gt(ROSA)26Sor⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1 * ICR

skeleton

abnormal bone structure ( J:156474 )

• bones are abnormally ossified and hypervascularized compared to in wild-type mice

abnormal bone ossification ( J:156474 )

Genotype
MGI:5432007

cn39

• Allelic Composition: Epas1^tm1Mcs/Epas1^tm1Mcs; Vhl^tm1Jae/Vhl^tm1Jae; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S4/SvJae * 129X1/SvJ * CD-1

hematopoietic system

hematopoietic system phenotype ( J:186085 )

N • mice exhibit normal hematocrit

homeostasis/metabolism

decreased circulating erythropoietin level ( J:186085 )

Genotype
MGI:5306892

cn40

• Allelic Composition: Casr^tm1Wch/Casr^tm1Wch; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

skeleton

skeleton phenotype ( J:180651 )

N • mice exhibit normal cortical bone thickness

decreased compact bone volume ( J:180651 )

abnormal trabecular bone morphology ( J:180651 )

• mice exhibit increased trabecular spacing compared with control mice

decreased trabecular bone volume ( J:180651 )

decreased bone trabecula number ( J:180651 )

decreased trabecular bone connectivity density ( J:180651 )

decreased trabecular bone thickness ( J:180651 )

abnormal skeleton development ( J:180651 )

• blocked, reduced bone formation

decreased bone mineralization ( J:180651 )

• undermineralized skeleton

growth/size/body

decreased body size ( J:180651 )

postnatal growth retardation ( J:180651 )

• blocked

Genotype
MGI:5521547

cn41

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0; Tg(tetO-RNAi:Trp53)ASlowe/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

mortality/aging

premature death ( J:199542 )

• mutants have a median survival of 401 days

neoplasm

increased metastatic potential ( J:199542 )

• 85.72% of mice show metastatic dissemination, commonly to the lung and liver

• high degrees of mineralization are apparent in primary and metastatic lesions

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 401 days

• 42.9% of tumors are found on the lower long bones, 42.9% of tumors are found on the mandible/head, and 14.3% of tumors are in other axial locations

• osteosarcoma is characterized by a uniform heavily mineralized osteoblastic (well differentiated) appearance in both primary and metastatic sites and osteosarcomas fail to become adipogenic under inductive conditions, indicating a cell population that is osteoblast restricted

• tumors resemble human osteoblastic osteosarcoma

• osteosarcomas exhibit clonal cytogenic abnormalities and karyotypic complexity; most frequent changes are recurrent gains of chromosomes 14 and 15 and loss of chromosomes 3, 7, and 12, as well as inter-chromosomal rearrangement involving chromosomes 6, 8, and 15

• however, nonosteoblastic lineage sarcomas or hibernomas are not seen in mutants

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:199542 )

• increase in serum alkaline phosphatase levels

skeleton

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 401 days

• 42.9% of tumors are found on the lower long bones, 42.9% of tumors are found on the mandible/head, and 14.3% of tumors are in other axial locations

• osteosarcoma is characterized by a uniform heavily mineralized osteoblastic (well differentiated) appearance in both primary and metastatic sites and osteosarcomas fail to become adipogenic under inductive conditions, indicating a cell population that is osteoblast restricted

• tumors resemble human osteoblastic osteosarcoma

• osteosarcomas exhibit clonal cytogenic abnormalities and karyotypic complexity; most frequent changes are recurrent gains of chromosomes 14 and 15 and loss of chromosomes 3, 7, and 12, as well as inter-chromosomal rearrangement involving chromosomes 6, 8, and 15

• however, nonosteoblastic lineage sarcomas or hibernomas are not seen in mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:199542

Genotype
MGI:5086012

cn42

• Allelic Composition: Amer1^tm1.1Nbar/Y; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL

craniofacial

large fontanelles ( J:173242 )

skeleton

abnormal bone structure ( J:173242 )

♂

increased bone volume ( J:173242 )

♂

increased osteoblast cell number ( J:173242 )

♂ • increase in the osteoblast number relative to surface area

increased trabecular bone thickness ( J:173242 )

♂

osteosclerosis ( J:173242 )

♂

abnormal skeleton development ( J:173242 )

♂

large fontanelles ( J:173242 )

increased bone mineralization ( J:173242 )

♂ • increased mineralization of cortical and trabecular bone

♂ • increased in bone mineralized surface per bone surface

♂ • however, no increase in bone width is detected

delayed fontanelle closure ( J:173242 )

♂ • wide cranial fontanelles are persistent until birth

increased bone ossification ( J:173242 )

♂ • increased bone formation rate per tissue volume

Genotype
MGI:5519098

cn43

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * CD-1

neoplasm

neoplasm ( J:136693 )

N • mice do not develop osteosarcoma over 18 months

Genotype
MGI:5432002

cn44

• Allelic Composition: Vhl^tm1Jae/Vhl^tm1Jae; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S4/SvJae * CD-1

hematopoietic system

enlarged spleen ( J:186085 )

abnormal blood cell morphology/development ( J:186085 )

• 3-fold increase in the frequency of KLS cells (hematopoietic stem cells and multipotential progenitors)

extramedullary hematopoiesis ( J:186085 )

decreased bone marrow cell number ( J:186085 )

increased erythroid progenitor cell number ( J:186085 )

• 1.4-fold in the bone marrow

• 4-fold in the spleen

• increased mature erythroid (CFU-E) compared with immature erythroid (BFU-E)

increased erythrocyte cell number ( J:186085 )

polycythemia ( J:186085 )

• severe by 2 months

increased hematocrit ( J:186085 )

decreased lymphocyte cell number ( J:186085 )

increased hematopoietic stem cell number ( J:186085 )

skeleton

increased trabecular bone volume ( J:186085 )

• 2.5-fold in the metaphyseal region

increased osteoblast cell number ( J:186085 )

• increased trabecular osteoblasts

increased bone trabecula number ( J:186085 )

increased trabecular bone mass ( J:186085 )

• in the metaphyseal and diaphyseal regions

cardiovascular system

abnormal angiogenesis ( J:186085 )

• hypervasculatization of the bone

growth/size/body

decreased body size ( J:186085 )

enlarged spleen ( J:186085 )

homeostasis/metabolism

increased circulating erythropoietin level ( J:186085 )

immune system

enlarged spleen ( J:186085 )

decreased lymphocyte cell number ( J:186085 )

limbs/digits/tail

abnormal foot pad morphology ( J:186085 )

• red paw

Genotype
MGI:7281134

cn45

• Allelic Composition: Mbtps1^tm1Jdh/Mbtps1^tm1Jdh; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CD-1

cellular

increased chondrocyte apoptosis ( J:258274 )

• at P7 in the epiphyseal cartilage

growth/size/body

decreased body size ( J:258274 )

• dwarfed mice with fragile bones

hematopoietic system

abnormal bone marrow cell morphology/development ( J:258274 )

• decrease in the ability of bone marrow stem cells to form colony-forming unit-fibroblasts

• dramatic decrease in the number of mesenchymal-derived skeletal stem cells

skeleton

increased chondrocyte apoptosis ( J:258274 )

• at P7 in the epiphyseal cartilage

abnormal appendicular skeleton morphology ( J:258274 )

• smaller appendicular elements

abnormal axial skeleton morphology ( J:258274 )

• smaller axial elements

scoliosis ( J:258274 )

• varying degrees of scoliosis that can be severe and is seen as early as 7-10 days of age

decreased bone mineral density ( J:258274 )

• severe at P1 and P7

decreased volumetric bone mineral density ( J:258274 )

• in trabecular and cortical bone at P7

decreased compact bone volume ( J:258274 )

• decreased bone volume fraction at P7

decreased trabecular bone volume ( J:258274 )

• decrease in bone volume fraction

decreased compact bone thickness ( J:258274 )

• mid-diaphyseal cortical bone is smaller in width with thinner cortical bone

decreased osteoblast cell number ( J:258274 )

• decreased on the endosteal surface of the cortical bone

abnormal skeleton development ( J:258274 )

• at E15.5 and E16.5 in endochondral bone only cartilage is seen where the primary ossification center would normally be with no sign of vascular invasion

• dramatic decrease in the number of mesenchymal-derived skeletal stem cells in the bone marrow

decreased width of hypertrophic chondrocyte zone ( J:258274 )

• smaller

abnormal bone ossification ( J:258274 )

• osteogenic capacity of bone marrow stem cells is absent in vitro

decreased bone mineralization ( J:258274 )

• decrease in bone mineral apposition rate and bone formation rate/bone surface

delayed endochondral bone ossification ( J:258274 )

• at E15.5 and E16.5 only cartilage is seen where the primary ossification center would normally be with no sign of vascular invasion

• at P7 and P10, the secondary ossification center in the epiphyseal cartilage is absent

fragile skeleton ( J:258274 )

• drastic reduction in pMOI (a measure of resistance to torsional force)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic scoliosis		DOID:0060250		J:258274

Genotype
MGI:7281135

cn46

• Allelic Composition: Mbtps1^tm1Jdh/Mbtps1⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CD-1

growth/size/body

decreased body size ( J:258274 )

• heterozygous mice are smaller than wild-type or recombinase expressing controls but larger than homozygous mice

skeleton

abnormal appendicular skeleton morphology ( J:258274 )

• smaller appendicular elements, intermediate to homozygous mice

abnormal axial skeleton morphology ( J:258274 )

• smaller axial elements, intermediate to homozygous mice

abnormal compact bone thickness ( J:258274 )

• mid-diaphyseal cortical bone is smaller in width but not reduced in thickness

abnormal bone ossification ( J:258274 )

• osteogenic capacity of bone marrow stem cells is absent in vitro

Genotype
MGI:5604139

cn47

• Allelic Composition: Smad4^tm2.1Cxd/Smad4^tm2.1Cxd; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CD-1

mortality/aging

premature death ( J:211171 )

• almost none of the mutants survive to 8 weeks

• lethality is not alleviated by paste-formula food or by keeping pups with the mother

postnatal lethality, incomplete penetrance ( J:211171 )

• about 50% of pups die by P14 and almost none survive to 8 weeks

skeleton

abnormal osteoblast physiology ( J:211171 )

• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

abnormal tibia morphology ( J:211171 )

• tibia are small but morphologically normal

decreased diameter of tibia ( J:211171 )

• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls

short tibia ( J:211171 )

• at P28, tibias are about 22% shorter relative to controls

clavicle hypoplasia ( J:211171 )

abnormal long bone diaphysis morphology ( J:211171 )

• diaphyseal medullary space is inappropriately populated by an excessive amount of trabecular bone

rib fractures ( J:211171 )

• multiple rib fractures are seen at 8 weeks of age

abnormal bone collagen fibril morphology ( J:211171 )

• marker analysis indicates abnormal thickness or packing density of collagen fibers in tibia and delayed differentiation of osteoblasts

decreased bone mineral density ( J:211171 )

• craniofacial and axial skeleton are severely under mineralized

• bone mineral density in P28 tibias is reduced 20% relative to controls

• hypomineralized interparietal bones

abnormal compact bone lamellar structure ( J:211171 )

• cortical bone is primarily woven rather than lamellar

decreased compact bone thickness ( J:211171 )

• cortical thickness is decreased by 15%

abnormal osteocyte morphology ( J:211171 )

• osteocyte density is increased in the cortex of bones, but no differences in cancellous bone

abnormal trabecular bone morphology ( J:211171 )

• trabecular bone populates the entire diaphysis instead of being restricted to primary and secondary ossification centers

• trabecular structures in the diaphysis of tibiae are bone and not cartilage left behind during resorption of endochondral cartilage template

delayed bone ossification ( J:211171 )

craniofacial

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

growth/size/body

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

small thoracic cavity ( J:211171 )

decreased body size ( J:211171 )

• pups are slightly smaller at birth and mice are severely runted by P28

hematopoietic system

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

immune system

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

limbs/digits/tail

abnormal tibia morphology ( J:211171 )

• tibia are small but morphologically normal

decreased diameter of tibia ( J:211171 )

• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls

short tibia ( J:211171 )

• at P28, tibias are about 22% shorter relative to controls

cellular

abnormal osteoblast physiology ( J:211171 )

• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta		DOID:12347	OMIM:PS166200	J:211171

Genotype
MGI:5604140

cn48

• Allelic Composition: Smad4^tm2.1Cxd/Smad4⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CD-1

craniofacial

malocclusion ( J:211171 )

• mice develop oral malocclusion

skeleton

malocclusion ( J:211171 )

• mice develop oral malocclusion

increased compact bone thickness ( J:211171 )

• cortical thickness is 23% higher

growth/size/body

malocclusion ( J:211171 )

• mice develop oral malocclusion

Genotype
MGI:5432008

cn49

• Allelic Composition: Egln1^tm2Fong/Egln1^tm2Fong; Egln2^tm2Fong/Egln2^tm2Fong; Egln3^tm2Fong/Egln3^tm2Fong; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCr * CD-1

hematopoietic system

increased hematocrit ( J:186085 )

Genotype
MGI:5544624

cn50

• Allelic Composition: Cthrc1^tm1.1Suna/Cthrc1^tm1.1Suna; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NTac * CD-1

skeleton

skeleton phenotype ( J:201631 )

N • mice exhibit normal bone mass

Genotype
MGI:3689417

cn51

• Allelic Composition: Smo^tm1Amc/Smo^tm2Amc; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129X1/SvJ * CD-1

normal phenotype

no abnormal phenotype detected ( J:114494 )

• mutants show normal program of chondrocyte and osteoblast development

Genotype
MGI:5698049

cn52

• Allelic Composition: Evc2^tm2.1Mis/Evc2^tm2.1Mis; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129X1/SvJ * CD-1

growth/size/body

growth/size/body region phenotype ( J:226455 )

N • no overt differences in body weight compared to controls

skeleton

skeleton phenotype ( J:226455 )

N • no overt phenotypes in skeletal system at 6 months after birth compared to controls

N • no overt differences in lengths of long bones compared to controls and no overt changes in trabecular components and cortical components of tibia

Genotype
MGI:3689416

cn53

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129X1/SvJ * CD-1

mortality/aging

perinatal lethality, complete penetrance ( J:114494 )

• mutants die at birth

limbs/digits/tail

short limbs ( J:114494 )

• from E14.5 - P0, examination shows that limbs are shorter than in wild-type

skeleton

abnormal osteoblast differentiation ( J:114494 )

• expansion of Osx1 expression (Osx1-expressing cells) at E14.5, indicating promotion of osteoblast development, is observed

• no Oc+ terminal osteoblasts are found prior to E16.5, and few that are observed are restricted to periosteal region

abnormal osteoclast differentiation ( J:114494 )

• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type

abnormal long bone epiphyseal plate morphology ( J:114494 )

• at E14.5 and 16.5, tibia has abnormal wedge-shaped growth plate with few identifiable hypertrophic chondrocytes visible compared to wild-type

abnormal trabecular bone morphology ( J:114494 )

• at E16.5, no primary spongiosa-like matrix is observed in mutants, unlike wild-type; matrix resembles dense matrix restricted to region forming bone collar

abnormal bone ossification ( J:114494 )

• at E16.5, long bones appear to have a more intense and broader ossification center than in wild-type

• at P0, a thick bony matrix characterizes all long bones; bone formation is apparent in several cranial regions

• at E14.5, osteoblast lineage is expanded and 3-fold increase in proliferation of osteoblast-forming regions along the length of the periosteum

premature endochondral bone ossification ( J:114494 )

• at E14.5, extensive premature bone ossification of the tibia is seen, while no mineralization in wild-type has occurred

delayed intramembranous bone ossification ( J:114494 )

• delayed ossification in skull bones is apparent at E16.5

hematopoietic system

abnormal osteoclast differentiation ( J:114494 )

• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type

immune system

abnormal osteoclast differentiation ( J:114494 )

• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type

cellular

abnormal osteoblast differentiation ( J:114494 )

• expansion of Osx1 expression (Osx1-expressing cells) at E14.5, indicating promotion of osteoblast development, is observed

• no Oc+ terminal osteoblasts are found prior to E16.5, and few that are observed are restricted to periosteal region

abnormal osteoclast differentiation ( J:114494 )

• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type

Genotype
MGI:5520089

cn54

• Allelic Composition: Mmp14^tm1Stjw/Mmp14^tm1Stjw; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: C57BL/6 * CD-1

skeleton

skeleton phenotype ( J:198679 )

N • mice exhibit normal chondrogenesis

decreased bone mineral density ( J:198679 )

delayed intramembranous bone ossification ( J:198679 )

delayed cranial suture closure ( J:198679 )

adipose tissue

adipose tissue phenotype ( J:198679 )

N • mice exhibit normal adipogenesis

Genotype
MGI:4452404

cn55

• Allelic Composition: Sbds^tm1Dats/Sbds^tm1Dats; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: C57BL/6 * CD-1

hematopoietic system

impaired hematopoiesis ( J:158901 )

• mice exhibit intrameduallry apoptosis of hematopoeitic progenitor cells unlike in wild-type mice

abnormal megakaryocyte morphology ( J:158901 )

• micro-megakaryocytes

decreased leukocyte cell number ( J:158901 )

decreased lymphocyte cell number ( J:158901 )

• but not neutropenia

decreased B cell number ( J:158901 )

• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice

abnormal myeloid leukocyte morphology ( J:158901 )

• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice

abnormal neutrophil morphology ( J:158901 )

skeleton

abnormal bone structure ( J:158901 )

• texture of mineralized is altered compared to in wild-type mice

abnormal bone marrow morphology ( J:158901 )

• bone marrow vascularity is increased compared to in wild-type mice

cardiovascular system

abnormal cardiovascular system morphology ( J:158901 )

• bone marrow vascularity is increased compared to in wild-type mice

immune system

decreased leukocyte cell number ( J:158901 )

decreased lymphocyte cell number ( J:158901 )

• but not neutropenia

decreased B cell number ( J:158901 )

• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice

abnormal myeloid leukocyte morphology ( J:158901 )

• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice

abnormal neutrophil morphology ( J:158901 )

Genotype
MGI:3831756

cn56

• Allelic Composition: Nfatc1^tm3Glm/Nfatc1^tm3Glm; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?
• Genetic Background: involves: C57BL/6 * CD-1

skeleton

skeleton phenotype ( J:144598 )

N • mice do not display an osteopetrotic phenotype

Genotype
MGI:6256537

cn57

• Allelic Composition: Usp34^em1Qyn/Usp34^em1Qyn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: C57BL/6J * CD-1

skeleton

decreased bone mineral density of femur ( J:266454 )

decreased volumetric bone mineral density ( J:266454 )

decreased osteoblast cell number ( J:266454 )

decreased bone trabecula number ( J:266454 )

increased bone trabecular spacing ( J:266454 )

decreased bone mineralization ( J:266454 )

decreased bone ossification ( J:266454 )

Genotype
MGI:6150914

cn58

• Allelic Composition: Rnf146^tm1.1Rtpl/Rnf146^tm1.1Rtpl; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: C57BL/6J * CD-1

mortality/aging

neonatal lethality, complete penetrance ( J:244583 )

• mice die shortly after birth due to respiratory distress

skeleton

skeleton phenotype ( J:244583 )

N • mice exhibit normal major and minor bone diameter and periosteal and endosteal perimeter

N • mice exhibit normal osteoclast number and function

increased bone marrow adipose tissue amount ( J:244583 )

• 40-fold in tibial bone marrow fat stores

impaired osteoblast differentiation ( J:244583 )

decreased osteoblast proliferation ( J:244583 )

large anterior fontanelle ( J:244583 )

• with calvarial hypomineralization

large posterior fontanelle ( J:244583 )

• with calvarial hypomineralization

abnormal alveolar process morphology ( J:244583 )

• hypoplasia of the periodontal alveolar bone and enamel

abnormal ameloblast differentiation ( J:244583 )

• loss of polarization

abnormal limb long bone morphology ( J:244583 )

• severely hypoplastic

clavicle hypoplasia ( J:244583 )

abnormal rib morphology ( J:244583 )

• severely hypoplastic

decreased bone mineral density ( J:244583 )

• in trabecular bone

decreased compact bone volume ( J:244583 )

decreased trabecular bone volume ( J:244583 )

decreased compact bone thickness ( J:244583 )

decreased osteoblast cell number ( J:244583 )

decreased bone trabecula number ( J:244583 )

• however, trabecular thickness is normal

increased bone trabecular spacing ( J:244583 )

decreased bone mineralization ( J:244583 )

• calvarial hypomineralization, which is more severe than in Tg(Sp7-tTA,tetO-EGFP/cre)1Amc hemizygous mice

abnormal endochondral bone ossification ( J:244583 )

• impaired

• however, chondrocyte differentiation is normal

abnormal intramembranous bone ossification ( J:244583 )

decreased bone ossification ( J:244583 )

homeostasis/metabolism

decreased insulin secretion ( J:244583 )

• reduced production

increased circulating glucose level ( J:244583 )

decreased circulating insulin level ( J:244583 )

• defective glucose-stimulated insulin secretion

decreased circulating osteocalcin level ( J:244583 )

• reduced undercarboxylated osteocalcin serum levels

increased circulating triglyceride level ( J:244583 )

impaired glucose tolerance ( J:244583 )

adipose tissue

increased total body fat amount ( J:244583 )

• 2-fold

increased bone marrow adipose tissue amount ( J:244583 )

• 40-fold in tibial bone marrow fat stores

growth/size/body

abnormal alveolar process morphology ( J:244583 )

• hypoplasia of the periodontal alveolar bone and enamel

abnormal ameloblast differentiation ( J:244583 )

• loss of polarization

respiratory system

respiratory distress ( J:244583 )

endocrine/exocrine glands

decreased pancreatic islet number ( J:244583 )

small pancreatic islets ( J:244583 )

decreased insulin secretion ( J:244583 )

• reduced production

cellular

impaired osteoblast differentiation ( J:244583 )

decreased osteoblast proliferation ( J:244583 )

craniofacial

large anterior fontanelle ( J:244583 )

• with calvarial hypomineralization

large posterior fontanelle ( J:244583 )

• with calvarial hypomineralization

abnormal alveolar process morphology ( J:244583 )

• hypoplasia of the periodontal alveolar bone and enamel

abnormal ameloblast differentiation ( J:244583 )

• loss of polarization

limbs/digits/tail

abnormal limb long bone morphology ( J:244583 )

• severely hypoplastic

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteochondrodysplasia		DOID:2256		J:244583

Genotype
MGI:7491815

cn59

• Allelic Composition: Chd7^em1Kangn/Chd7^em1Kangn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: C57BL/6J * CD-1

mortality/aging

premature death ( J:336448 )

• relatively lower survival rate

growth/size/body

decreased body size ( J:336448 )

• smaller size and delayed growth features compared to controls

decreased body weight ( J:336448 )

skeleton

increased bone marrow adipose tissue amount ( J:336448 )

• increase in bone marrow adipose tissue accumulation in both primary and secondary ossification centers

• phenotype is more remarkable in the tibia, with considerable marrow adipose tissue in the mesial region and the distal region is mostly occupied by adipose tissue

abnormal compact bone morphology ( J:336448 )

• diminished cortical bone

decreased osteoblast cell number ( J:336448 )

abnormal trabecular bone morphology ( J:336448 )

• diminished trabecular bone

decreased bone mass ( J:336448 )

decreased bone mineralization ( J:336448 )

• slower bone mineral apposition rate at 4 weeks of age

decreased bone ossification ( J:336448 )

• slower bone formation rate

adipose tissue

increased bone marrow adipose tissue amount ( J:336448 )

• increase in bone marrow adipose tissue accumulation in both primary and secondary ossification centers

• phenotype is more remarkable in the tibia, with considerable marrow adipose tissue in the mesial region and the distal region is mostly occupied by adipose tissue

Genotype
MGI:5689563

cn60

• Allelic Composition: Runx3^tm3Yg/Runx3^tm3Yg; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: CD-1

mortality/aging

decreased survivor rate ( J:224290 )

• low survival rates

growth/size/body

decreased body size ( J:224290 )

• severe congenital dwarfism

Genotype
MGI:5492068

cn61

• Allelic Composition: Ctsk^tm1.1Rbar/Ctsk^tm1.1Rbar; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: CD-1

Increase in cross-sectional bone volume and cortical bone volume in Ctsk^tm1.1Rbar/Ctsk^tm1.1Rbar Tg(Itgam-cre)AJva/0 femurs but not in Ctsk^tm1.1Rbar/Ctsk^tm1.1Rbar Tg(Mx1-cre)1Cgn/0 or Ctsk^tm1.1Rbar/Ctsk^tm1.1Rbar Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0 femurs

skeleton

skeleton phenotype ( J:194492 )

N • mice exhibit normal bone density

Genotype
MGI:5613581

cn62

• Allelic Composition: Gt(ROSA)26Sor^{tm4(Wnt7b)Flng}/Gt(ROSA)26Sor⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: CD-1

skeleton

abnormal long bone morphology ( J:208766 )

• at E16.5 display a much thicker bone collar and no bone marrow

decreased length of long bones ( J:208766 )

abnormal bone structure ( J:208766 )

abnormal bone marrow cavity morphology ( J:208766 )

• at E16.5 the marrow region is occupied by cells that appear to be preosteoblasts and no marrow cavity is formed

• at E18.5 the marrow region is populated by mature osteoblasts

increased bone mineral density ( J:208766 )

• profoundly dense bones throughout the body at 2 months of age

increased osteoblast cell number ( J:208766 )

• at E18.5 the marrow region is populated by mature osteoblasts

increased bone mass ( J:208766 )

• at E18.5 and 2 months of age

• when cre expression is suppressed by doxycycline treatment until 1 month of age mice show a profound high bone mass phenotype at 2 months of age

delayed chondrocyte differentiation ( J:208766 )

• slight delay in chondrocyte maturation at E14.5

Genotype
MGI:5586499

cx63

• Allelic Composition: Col1a1^{tm2(tetO-Fosl2,-DsRed)Wag}/Col1a1⁺; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

cellular

abnormal osteoblast physiology ( J:211215 )

skeleton

abnormal osteoblast physiology ( J:211215 )

abnormal osteoclast morphology ( J:211215 )

• decreased osteoclast surface

increased bone volume ( J:211215 )

abnormal osteoblast morphology ( J:211215 )

• increased osteoblast surface

increased bone trabecula number ( J:211215 )

increased trabecular bone thickness ( J:211215 )

increased bone ossification ( J:211215 )

• increased bone formation

homeostasis/metabolism

decreased insulin secretion ( J:211215 )

• in response to glucose stimulation

• in the pancreas

decreased circulating glucose level ( J:211215 )

• in mice fed a normal diet or a high fat diet

• however, infection with Adipoq-expressing adenovirus rescues serum glucose levels in mice fed a normal or high fat diet

decreased circulating insulin level ( J:211215 )

• in fasted mice fed a normal diet

• in mice fed a normal diet or a high fat diet

• however, bone insulin levels are normal and infection with Adipoq-expressing adenovirus rescues levels in mice fed a normal, but not high fat, diet

increased circulating osteocalcin level ( J:211215 )

improved glucose tolerance ( J:211215 )

• in mice fed a normal diet or high fat diet

• however, infection with Adipoq-expressing adenovirus restores glucose tolerance in mice fed a normal diet

increased insulin sensitivity ( J:211215 )

• in mice fed a normal diet or high fat diet

• however, infection with Adipoq-expressing adenovirus restores insulin sensitivity in mice fed a normal diet

decreased circulating adiponectin level ( J:211215 )

growth/size/body

decreased body weight ( J:211215 )

• under normal diet and high fat diet conditions

• however, infection with Adipoq-expressing adenovirus rescues body weight in mice fed a normal, but not high fat, diet

endocrine/exocrine glands

decreased insulin secretion ( J:211215 )

• in response to glucose stimulation

• in the pancreas

adipose tissue

adipose tissue phenotype ( J:211215 )

N • mice exhibit normal adipocyte number and size

decreased gonadal fat pad weight ( J:211215 )

• under normal diet and high fat diet conditions

• however, infection with Adipoq-expressing adenovirus rescues fat pad weight in mice fed a normal or high fat diet

hematopoietic system

abnormal osteoclast morphology ( J:211215 )

• decreased osteoclast surface

immune system

abnormal osteoclast morphology ( J:211215 )

• decreased osteoclast surface

Genotype
MGI:5521546

cx64

• Allelic Composition: Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0; Tg(tetO-RNAi:Trp53)ASlowe/0
• Genetic Background: involves: C57BL/6 * CD-1

mortality/aging

premature death ( J:199542 )

• median survival is 485 days of age

neoplasm

increased metastatic potential ( J:199542 )

• 83.3% of mice show metastatic dissemination, commonly to the lung and liver

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 485 days

• 66.7% of tumors are in the long bones, 16.7% of tumors are found in the mandible/head, and 16.7% of tumors are in other axial locations

• osteosarcoma is characterized by a uniform heavily mineralized osteoblastic (well differentiated) appearance in both primary and metastatic sites and osteosarcomas fail to become adipogenic under inductive conditions, indicating a cell population that is osteoblast restricted

• tumors resemble human osteoblastic osteosarcoma

skeleton

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 485 days

• 66.7% of tumors are in the long bones, 16.7% of tumors are found in the mandible/head, and 16.7% of tumors are in other axial locations

• osteosarcoma is characterized by a uniform heavily mineralized osteoblastic (well differentiated) appearance in both primary and metastatic sites and osteosarcomas fail to become adipogenic under inductive conditions, indicating a cell population that is osteoblast restricted

• tumors resemble human osteoblastic osteosarcoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:199542

Genotype
MGI:5604141

tg65

• Allelic Composition: Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: CD-1

limbs/digits/tail

decreased diameter of tibia ( J:211171 )

• tibias are about 25% narrower at the mid-diaphysis compared to wild-type mice

short tibia ( J:211171 )

• about 7% decrease in tibia length

skeleton

decreased diameter of tibia ( J:211171 )

• tibias are about 25% narrower at the mid-diaphysis compared to wild-type mice

short tibia ( J:211171 )

• about 7% decrease in tibia length

decreased trabecular bone volume ( J:211171 )

• trabecular bone volume in the metaphysis is reduced by about 36%, although this doesnt reach statistical significance

increased compact bone thickness ( J:211171 )

• cortical thickness is increased by about 14.5%