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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc
transgene insertion 1, Andrew P McMahon
MGI:3689350
Summary 46 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N MGI:5519099
cn2
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53+
involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N MGI:5519100
cn3
Dicer1tm1Mmk/Dicer1tm1Mmk
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129 * C57BL/6 * CD-1 MGI:4452405
cn4
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1 MGI:5521545
cn5
Rb1tm3Tyj/Rb1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53+
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N MGI:5519097
cn6
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N MGI:5519094
cn7
Rb1tm3Tyj/Rb1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N MGI:5519095
cn8
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53+
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N MGI:5519096
cn9
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
involves: 129P2/OlaHsd * C57BL/6 * CD-1 MGI:5521544
cn10
Fosl2tm2Wag/Fosl2tm2Wag
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129P2/OlaHsd * C57BL/6 * CD-1 MGI:5586500
cn11
Cxcl12tm1Tng/Cxcl12tm1.1Link
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129P2/OlaHsd * C57BL/6 * CD-1 * FVB/N MGI:5468941
cn12
Pkd1tm3Jzh/Pkd1tm3Jzh
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?
involves: 129P2/OlaHsd * CD-1 MGI:3811610
cn13
Tnfsf11tm1.1Caob/Tnfsf11tm1.1Caob
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S * 129X1/SvJ * C57BL/6 * CD-1 MGI:5297382
cn14
Epas1tm1Mcs/Epas1tm1Mcs
Hif1atm3Rsjo/Hif1atm3Rsjo
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1 MGI:5432005
cn15
Hif1atm3Rsjo/Hif1atm3Rsjo
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1 MGI:5432006
cn16
Fbn1tm1.1Itl/Fbn1tm3Rmz
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J * CD-1 MGI:5439642
cn17
Ctnnb1tm1Max/Ctnnb1tm2Kem
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:3689415
cn18
Epas1tm1Mcs/Epas1tm1Mcs
Hif1atm3Rsjo/Hif1atm3Rsjo
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:5432003
cn19
Epas1tm1Mcs/Epas1tm1Mcs
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:5432004
cn20
Gt(ROSA)26Sortm4(Wnt7b)Flng/Gt(ROSA)26Sor+
Rptortm1Rueg/Rptortm1Rueg
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:5613582
cn21
Gt(ROSA)26Sortm4(Wnt7b)Flng/Gt(ROSA)26Sor+
Rptortm1Rueg/Rptor+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:5613583
cn22
Gt(ROSA)26Sortm1(Vegfa*)Jhai/Gt(ROSA)26Sor+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * CD-1 * ICR MGI:4429124
cn23
Epas1tm1Mcs/Epas1tm1Mcs
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S4/SvJae * 129X1/SvJ * CD-1 MGI:5432007
cn24
Casrtm1Wch/Casrtm1Wch
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S4/SvJae * C57BL/6 * CD-1 MGI:5306892
cn25
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Tg(tetO-RNAi:Trp53)ASlowe/0
involves: 129S4/SvJae * C57BL/6 * CD-1 MGI:5521547
cn26
Amer1tm1.1Nbar/Y
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL MGI:5086012
cn27
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S4/SvJae * C57BL/6J * CD-1 MGI:5519098
cn28
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S4/SvJae * CD-1 MGI:5432002
cn29
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6J * CD-1 MGI:5604139
cn30
Smad4tm2.1Cxd/Smad4+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6J * CD-1 MGI:5604140
cn31
Egln1tm2Fong/Egln1tm2Fong
Egln2tm2Fong/Egln2tm2Fong
Egln3tm2Fong/Egln3tm2Fong
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6NCr * CD-1 MGI:5432008
cn32
Cthrc1tm1.1Suna/Cthrc1tm1.1Suna
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6NTac * CD-1 MGI:5544624
cn33
Evc2tm2.1Mis/Evc2tm2.1Mis
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129X1/SvJ * CD-1 MGI:5698049
cn34
Ctnnb1tm1Mmt/Ctnnb1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129X1/SvJ * CD-1 MGI:3689416
cn35
Smotm1Amc/Smotm2Amc
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129X1/SvJ * CD-1 MGI:3689417
cn36
Sbdstm1Dats/Sbdstm1Dats
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: C57BL/6 * CD-1 MGI:4452404
cn37
Nfatc1tm3Glm/Nfatc1tm3Glm
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?
involves: C57BL/6 * CD-1 MGI:3831756
cn38
Mmp14tm1Stjw/Mmp14tm1Stjw
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: C57BL/6 * CD-1 MGI:5520089
cn39
Rnf146tm1.1Rtpl/Rnf146tm1.1Rtpl
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: C57BL/6J * CD-1 MGI:6150914
cn40
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Usp34em1Qyn/Usp34em1Qyn
involves: C57BL/6J * CD-1 MGI:6256537
cn41
Ctsktm1.1Rbar/Ctsktm1.1Rbar
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: CD-1 MGI:5492068
cn42
Gt(ROSA)26Sortm4(Wnt7b)Flng/Gt(ROSA)26Sor+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: CD-1 MGI:5613581
cn43
Runx3tm3Yg/Runx3tm3Yg
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: CD-1 MGI:5689563
cx44
Col1a1tm2(tetO-Fosl2,-DsRed)Wag/Col1a1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
involves: 129S4/SvJae * C57BL/6 * CD-1 MGI:5586499
cx45
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Tg(tetO-RNAi:Trp53)ASlowe/0
involves: C57BL/6 * CD-1 MGI:5521546
tg46
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
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• complete penetrance of osteosarcomas with an average latency of 292 days

mortality/aging
• mice die from around 250 to 375 days of age

neoplasm
• tumors show metastasis, most frequently to the lung and then the liver
• complete penetrance of osteosarcomas with an average latency of 292 days




Genotype
MGI:5519100
cn2
Allelic
Composition
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53+
Genetic
Background
involves: 129 * 129P2/OlaHsd * C57BL/6J * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• low penetrance (8.33%) of osteosarcomas with a long latency of 338 days of age on average

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




Genotype
MGI:4452405
cn3
Allelic
Composition
Dicer1tm1Mmk/Dicer1tm1Mmk
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129 * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Mmk mutation (0 available); any Dicer1 mutation (70 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice with tumors die by 4 to 5 weeks of age
• 30% of mice die by 8 weeks of age

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

hematopoietic system
N
• mice exhibit normal frequency and function of hematopoietic stem cells and progenitors
• mice with myeloid sarcomas exhibit increased spleen weight with blast cell infiltration unlike in wild-type mice
• in the spleen of some mice
• profound in some mice
• 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
• micro-megakaryocytes with hypolobulated, hyperchromatic nuclei in the bone marrow
• profound in some mice
• giant platelets in the blood
• with all subsets of leukocytes exhibiting decreased numbers
• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice
• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice
• hypersegementation

skeleton
• texture of mineralized is altered compared to in wild-type mice
• however, trabecular and cortical bone volumes are normal
• bone marrow vascularity is increased compared to in wild-type mice
• 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
• at 2 to 3 weeks of age, mice develop facial tumors
• at 2 to 3 weeks of age, mice develop myeoblastic tumors
• mice exhibit sporadic acute myelogenous leukemia unlike wild-type mice
• mice exhibit sporadic myeloid sarcoma with infiltration behavior unlike wild-type mice

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

growth/size/body
• at 2 to 3 weeks of age, mice develop facial tumors
• mice with myeloid sarcomas exhibit increased spleen weight with blast cell infiltration unlike in wild-type mice

immune system
• mice with myeloid sarcomas exhibit increased spleen weight with blast cell infiltration unlike in wild-type mice
• with all subsets of leukocytes exhibiting decreased numbers
• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice
• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice
• hypersegementation

cellular




Genotype
MGI:5521545
cn4
Allelic
Composition
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm3Tyj mutation (10 available); any Rb1 mutation (84 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 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

mortality/aging
• mutants have a median survival of 127 days of age

neoplasm
• 20.6% of mice show metastatic dissemination, commonly to the lung and liver
• seen in one mutant
• 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:5519097
cn5
Allelic
Composition
Rb1tm3Tyj/Rb1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53+
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm3Tyj mutation (10 available); any Rb1 mutation (84 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes

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

neoplasm
• tumors show metastasis, most frequently to the lung and then the liver
• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes




Genotype
MGI:5519094
cn6
Allelic
Composition
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm3Tyj mutation (10 available); any Rb1 mutation (84 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age
• lesions are seen as early as 2 months of age
• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra
• tumors exhibit a histology consistent with human medullary osteosarcoma
• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues
• metastasis is not seen but this may be due to rapid tumor development
• 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

mortality/aging
• mice begin to die around 95 days of age and all die by 161 days of age

growth/size/body
• slight growth delay that resolves with age

neoplasm
• about 20% of mice develop adipogenic tumors which occur on the outer chest or abdomen
• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age
• lesions are seen as early as 2 months of age
• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra
• tumors exhibit a histology consistent with human medullary osteosarcoma
• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues
• metastasis is not seen but this may be due to rapid tumor development
• 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

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




Genotype
MGI:5519095
cn7
Allelic
Composition
Rb1tm3Tyj/Rb1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm3Tyj mutation (10 available); any Rb1 mutation (84 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age

mortality/aging
• die from around 125 to 260 days of age

neoplasm
• tumors show metastasis, most frequently to the lung and then the liver
• 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:5519096
cn8
Allelic
Composition
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53+
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm3Tyj mutation (10 available); any Rb1 mutation (84 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age

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

neoplasm
• tumors show metastasis, most frequently to the lung and then the liver
• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age




Genotype
MGI:5521544
cn9
Allelic
Composition
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Trp53tm1Brn mutation (17 available); any Trp53 mutation (205 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 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
• mutants have a median survival of 226.5 days of age

neoplasm
• 50% of mice show metastatic dissemination, commonly to the lung and liver
• 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:5586500
cn10
Allelic
Composition
Fosl2tm2Wag/Fosl2tm2Wag
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fosl2tm2Wag mutation (0 available); any Fosl2 mutation (7 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• fewer mineralized nodules produced from primary osteoblasts under osteogenic conditions
• increased osteoclast surface
• decreased osteoblast surface
• decreased bone formation

cellular
• fewer mineralized nodules produced from primary osteoblasts under osteogenic conditions

homeostasis/metabolism
• in mice fed a high fat diet
• however, levels are normal in mice fed a normal diet
• in mice fed a normal diet and high fat diet
• in mice fed a high fat diet
• however, mice fed a normal diet exhibit insulin tolerance

growth/size/body
• under normal diet and high fat diet

adipose tissue
N
• mice exhibit normal adipocyte number and size
• under normal diet and high fat diet

hematopoietic system
• increased osteoclast surface

immune system
• increased osteoclast surface




Genotype
MGI:5468941
cn11
Allelic
Composition
Cxcl12tm1Tng/Cxcl12tm1.1Link
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cxcl12tm1.1Link mutation (1 available); any Cxcl12 mutation (21 available)
Cxcl12tm1Tng mutation (1 available); any Cxcl12 mutation (21 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• the numbers of colony-forming cells and KSL cells are increased in the blood and spleen, demonstrating constitutive HPC mobilization, compared with control mice
• in the bone marrow
• modest decrease in the absolute number
• increased cycling of more mature KSL progenitors in the blood
• however, hematopoietic stem cell cycling is normal

immune system
• in the bone marrow




Genotype
MGI:3811610
cn12
Allelic
Composition
Pkd1tm3Jzh/Pkd1tm3Jzh
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?
Genetic
Background
involves: 129P2/OlaHsd * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pkd1tm3Jzh mutation (0 available); any Pkd1 mutation (104 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• mice display a delay in intramembranous ossification
• however, no growth defects of the craniofacial bones are found




Genotype
MGI:5297382
cn13
Allelic
Composition
Tnfsf11tm1.1Caob/Tnfsf11tm1.1Caob
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S * 129X1/SvJ * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Tnfsf11tm1.1Caob mutation (1 available); any Tnfsf11 mutation (28 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
N
• mice treated with doxycycline until 4 months of age exhibit normal cancellous architecture at 6 months
• in all mice
• however, exposure to doxycycline restores tooth eruption
• at 5 weeks of age
• at 5 weeks of age
• mice exhibit unresorbed cartilage unlike wild-type mice
• widened growth plate in the femur

craniofacial
• in all mice
• however, exposure to doxycycline restores tooth eruption

growth/size/body
• in all mice
• however, exposure to doxycycline restores tooth eruption




Genotype
MGI:5432005
cn14
Allelic
Composition
Epas1tm1Mcs/Epas1tm1Mcs
Hif1atm3Rsjo/Hif1atm3Rsjo
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Epas1tm1Mcs mutation (1 available); any Epas1 mutation (50 available)
Hif1atm3Rsjo mutation (3 available); any Hif1a mutation (37 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Vhltm1Jae mutation (2 available); any Vhl mutation (13 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton

hematopoietic system
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




Genotype
MGI:5432006
cn15
Allelic
Composition
Hif1atm3Rsjo/Hif1atm3Rsjo
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hif1atm3Rsjo mutation (3 available); any Hif1a mutation (37 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Vhltm1Jae mutation (2 available); any Vhl mutation (13 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system

homeostasis/metabolism




Genotype
MGI:5439642
cn16
Allelic
Composition
Fbn1tm1.1Itl/Fbn1tm3Rmz
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fbn1tm1.1Itl mutation (1 available); any Fbn1 mutation (110 available)
Fbn1tm3Rmz mutation (1 available); any Fbn1 mutation (110 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype



Genotype
MGI:3689415
cn17
Allelic
Composition
Ctnnb1tm1Max/Ctnnb1tm2Kem
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctnnb1tm1Max mutation (0 available); any Ctnnb1 mutation (41 available)
Ctnnb1tm2Kem mutation (1 available); any Ctnnb1 mutation (41 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
limbs/digits/tail
• at E16.5, clear zones of hypertrophy are visible in limbs compared to controls

skeleton
• in mutant tibia, no Oc+ osteoblasts are detected, indicating failure of osteoblast progression to terminal osteoblasts
• hypertrophic chondrocytes line the periosteal region in addition to the normal growth plate
• membranous bone cranial ossification centers are absent at E18.5
• ossification in mutant periosteum of the tibia is absent
• 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
• in mutant tibia, no Oc+ osteoblasts are detected, indicating failure of osteoblast progression to terminal osteoblasts




Genotype
MGI:5432003
cn18
Allelic
Composition
Epas1tm1Mcs/Epas1tm1Mcs
Hif1atm3Rsjo/Hif1atm3Rsjo
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Epas1tm1Mcs mutation (1 available); any Epas1 mutation (50 available)
Hif1atm3Rsjo mutation (3 available); any Hif1a mutation (37 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
N
• mice exhibit normal hematopoietic stem cell frequency
• decreased frequency of CD71+/Ter119+ cells in the bone marrow

skeleton




Genotype
MGI:5432004
cn19
Allelic
Composition
Epas1tm1Mcs/Epas1tm1Mcs
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Epas1tm1Mcs mutation (1 available); any Epas1 mutation (50 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• decreased frequency of CD71+/Ter119+ cells in the bone marrow




Genotype
MGI:5613582
cn20
Allelic
Composition
Gt(ROSA)26Sortm4(Wnt7b)Flng/Gt(ROSA)26Sor+
Rptortm1Rueg/Rptortm1Rueg
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm4(Wnt7b)Flng mutation (0 available); any Gt(ROSA)26Sor mutation (745 available)
Rptortm1Rueg mutation (0 available); any Rptor mutation (87 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 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
• 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
• 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
cn21
Allelic
Composition
Gt(ROSA)26Sortm4(Wnt7b)Flng/Gt(ROSA)26Sor+
Rptortm1Rueg/Rptor+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm4(Wnt7b)Flng mutation (0 available); any Gt(ROSA)26Sor mutation (745 available)
Rptortm1Rueg mutation (0 available); any Rptor mutation (87 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• when cre expression is suppressed by doxycycline treatment until 1 month of age the marrow cavity is decreased
• 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
cn22
Allelic
Composition
Gt(ROSA)26Sortm1(Vegfa*)Jhai/Gt(ROSA)26Sor+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1 * ICR
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(Vegfa*)Jhai mutation (0 available); any Gt(ROSA)26Sor mutation (745 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• bones are abnormally ossified and hypervascularized compared to in wild-type mice




Genotype
MGI:5432007
cn23
Allelic
Composition
Epas1tm1Mcs/Epas1tm1Mcs
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S4/SvJae * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Epas1tm1Mcs mutation (1 available); any Epas1 mutation (50 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Vhltm1Jae mutation (2 available); any Vhl mutation (13 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
N
• mice exhibit normal hematocrit

homeostasis/metabolism




Genotype
MGI:5306892
cn24
Allelic
Composition
Casrtm1Wch/Casrtm1Wch
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Casrtm1Wch mutation (0 available); any Casr mutation (38 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
N
• mice exhibit normal cortical bone thickness
• mice exhibit increased trabecular spacing compared with control mice
• blocked, reduced bone formation
• undermineralized skeleton

growth/size/body




Genotype
MGI:5521547
cn25
Allelic
Composition
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Tg(tetO-RNAi:Trp53)ASlowe/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm3Tyj mutation (10 available); any Rb1 mutation (84 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Tg(tetO-RNAi:Trp53)ASlowe mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 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

mortality/aging
• mutants have a median survival of 401 days

neoplasm
• 85.72% of mice show metastatic dissemination, commonly to the lung and liver
• high degrees of mineralization are apparent in primary and metastatic lesions
• 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
• increase in serum alkaline phosphatase levels

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




Genotype
MGI:5086012
cn26
Allelic
Composition
Amer1tm1.1Nbar/Y
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amer1tm1.1Nbar mutation (0 available); any Amer1 mutation (3 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
craniofacial

skeleton
• increase in the osteoblast number relative to surface area
• increased mineralization of cortical and trabecular bone
• increased in bone mineralized surface per bone surface
• however, no increase in bone width is detected
• wide cranial fontanelles are persistent until birth
• increased bone formation rate per tissue volume




Genotype
MGI:5519098
cn27
Allelic
Composition
Rb1tm3Tyj/Rb1tm3Tyj
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6J * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rb1tm3Tyj mutation (10 available); any Rb1 mutation (84 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
N
• mice do not develop osteosarcoma over 18 months




Genotype
MGI:5432002
cn28
Allelic
Composition
Vhltm1Jae/Vhltm1Jae
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S4/SvJae * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Vhltm1Jae mutation (2 available); any Vhl mutation (13 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• 3-fold increase in the frequency of KLS cells (hematopoietic stem cells and multipotential progenitors)
• 1.4-fold in the bone marrow
• 4-fold in the spleen
• increased mature erythroid (CFU-E) compared with immature erythroid (BFU-E)
• severe by 2 months

skeleton
• 2.5-fold in the metaphyseal region
• increased trabecular osteoblasts
• in the metaphyseal and diaphyseal regions

cardiovascular system
• hypervasculatization of the bone

growth/size/body

homeostasis/metabolism

immune system

limbs/digits/tail




Genotype
MGI:5604139
cn29
Allelic
Composition
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6J * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (2 available); any Smad4 mutation (33 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

mortality/aging
• almost none of the mutants survive to 8 weeks
• lethality is not alleviated by paste-formula food or by keeping pups with the mother
• about 50% of pups die by P14 and almost none survive to 8 weeks

skeleton
• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix
• severe dental abnormalities
• underdeveloped incisors at P28
• yellow or even black dental discoloration typical of enamel hypoplasia
• mice develop oral malocclusion
• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones
• tibia are small but morphologically normal
• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls
• at P28, tibias are about 22% shorter relative to controls
• diaphyseal medullary space is inappropriately populated by an excessive amount of trabecular bone
• multiple rib fractures are seen at 8 weeks of age
• marker analysis indicates abnormal thickness or packing density of collagen fibers in tibia and delayed differentiation of osteoblasts
• craniofacial and axial skeleton are severely under mineralized
• bone mineral density in P28 tibias is reduced 20% relative to controls
• hypomineralized interparietal bones
• cortical bone is primarily woven rather than lamellar
• cortical thickness is decreased by 15%
• osteocyte density is increased in the cortex of bones, but no differences in cancellous bone
• 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

craniofacial
• severe dental abnormalities
• underdeveloped incisors at P28
• yellow or even black dental discoloration typical of enamel hypoplasia
• mice develop oral malocclusion

growth/size/body
• severe dental abnormalities
• underdeveloped incisors at P28
• yellow or even black dental discoloration typical of enamel hypoplasia
• mice develop oral malocclusion
• pups are slightly smaller at birth and mice are severely runted by P28

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

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

limbs/digits/tail
• tibia are small but morphologically normal
• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls
• at P28, tibias are about 22% shorter relative to controls

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




Genotype
MGI:5604140
cn30
Allelic
Composition
Smad4tm2.1Cxd/Smad4+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6J * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad4tm2.1Cxd mutation (2 available); any Smad4 mutation (33 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mice develop oral malocclusion

craniofacial
• mice develop oral malocclusion

skeleton
• mice develop oral malocclusion
• cortical thickness is 23% higher




Genotype
MGI:5432008
cn31
Allelic
Composition
Egln1tm2Fong/Egln1tm2Fong
Egln2tm2Fong/Egln2tm2Fong
Egln3tm2Fong/Egln3tm2Fong
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6NCr * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Egln1tm2Fong mutation (1 available); any Egln1 mutation (14 available)
Egln2tm2Fong mutation (1 available); any Egln2 mutation (14 available)
Egln3tm2Fong mutation (1 available); any Egln3 mutation (18 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system




Genotype
MGI:5544624
cn32
Allelic
Composition
Cthrc1tm1.1Suna/Cthrc1tm1.1Suna
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6NTac * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cthrc1tm1.1Suna mutation (1 available); any Cthrc1 mutation (21 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
N
• mice exhibit normal bone mass




Genotype
MGI:5698049
cn33
Allelic
Composition
Evc2tm2.1Mis/Evc2tm2.1Mis
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Evc2tm2.1Mis mutation (0 available); any Evc2 mutation (31 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
N
• no overt differences in body weight compared to controls

skeleton
N
• no overt phenotypes in skeletal system at 6 months after birth compared to controls
• 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
cn34
Allelic
Composition
Ctnnb1tm1Mmt/Ctnnb1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctnnb1tm1Mmt mutation (0 available); any Ctnnb1 mutation (41 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

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

skeleton
• 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
• at E16.5, osteoclasts are absent from mutants when they are detected normally in wild-type
• at E14.5 and 16.5, tibia has abnormal wedge-shaped growth plate with few identifiable hypertrophic chondrocytes visible compared to wild-type
• 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
• 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
• at E14.5, extensive premature bone ossification of the tibia is seen, while no mineralization in wild-type has occurred
• delayed ossification in skull bones is apparent at E16.5

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

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

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




Genotype
MGI:3689417
cn35
Allelic
Composition
Smotm1Amc/Smotm2Amc
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smotm1Amc mutation (1 available); any Smo mutation (30 available)
Smotm2Amc mutation (1 available); any Smo mutation (30 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• mutants show normal program of chondrocyte and osteoblast development




Genotype
MGI:4452404
cn36
Allelic
Composition
Sbdstm1Dats/Sbdstm1Dats
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sbdstm1Dats mutation (0 available); any Sbds mutation (28 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• mice exhibit intrameduallry apoptosis of hematopoeitic progenitor cells unlike in wild-type mice
• micro-megakaryocytes
• but not neutropenia
• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice
• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice

skeleton
• texture of mineralized is altered compared to in wild-type mice
• bone marrow vascularity is increased compared to in wild-type mice

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

immune system
• but not neutropenia
• B cell and B cell progenitors are decreased in the bone marrow compared to in wild-type mice
• myeloid cell frequency is increased in the bone marrow compared to in wild-type mice




Genotype
MGI:3831756
cn37
Allelic
Composition
Nfatc1tm3Glm/Nfatc1tm3Glm
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/?
Genetic
Background
involves: C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nfatc1tm3Glm mutation (1 available); any Nfatc1 mutation (29 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
N
• mice do not display an osteopetrotic phenotype




Genotype
MGI:5520089
cn38
Allelic
Composition
Mmp14tm1Stjw/Mmp14tm1Stjw
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mmp14tm1Stjw mutation (0 available); any Mmp14 mutation (29 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
N
• mice exhibit normal chondrogenesis

adipose tissue
N
• mice exhibit normal adipogenesis




Genotype
MGI:6150914
cn39
Allelic
Composition
Rnf146tm1.1Rtpl/Rnf146tm1.1Rtpl
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: C57BL/6J * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rnf146tm1.1Rtpl mutation (0 available); any Rnf146 mutation (14 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice die shortly after birth due to respiratory distress

skeleton
N
• mice exhibit normal major and minor bone diameter and periosteal and endosteal perimeter
• mice exhibit normal osteoclast number and function
• 40-fold in tibial bone marrow fat stores
• with calvarial hypomineralization
• with calvarial hypomineralization
• hypoplasia of the periodontal alveolar bone and enamel
• loss of polarization
• severely hypoplastic
• severely hypoplastic
• in trabecular bone
• however, trabecular thickness is normal
• calvarial hypomineralization, which is more severe than in Tg(Sp7-tTA,tetO-EGFP/cre)1Amc hemizygous mice
• impaired
• however, chondrocyte differentiation is normal

homeostasis/metabolism
• reduced production
• defective glucose-stimulated insulin secretion
• reduced undercarboxylated osteocalcin serum levels

adipose tissue
• 40-fold in tibial bone marrow fat stores

growth/size/body
• hypoplasia of the periodontal alveolar bone and enamel
• loss of polarization

respiratory system

endocrine/exocrine glands
• reduced production

cellular

craniofacial
• with calvarial hypomineralization
• with calvarial hypomineralization
• hypoplasia of the periodontal alveolar bone and enamel
• loss of polarization

limbs/digits/tail
• severely hypoplastic

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
cleidocranial dysplasia DOID:13994 OMIM:119600
OMIM:216330
J:244583




Genotype
MGI:6256537
cn40
Allelic
Composition
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Usp34em1Qyn/Usp34em1Qyn
Genetic
Background
involves: C57BL/6J * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Usp34em1Qyn mutation (0 available); any Usp34 mutation (136 available)
phenotype observed in females
phenotype observed in males
N normal phenotype



Genotype
MGI:5492068
cn41
Allelic
Composition
Ctsktm1.1Rbar/Ctsktm1.1Rbar
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctsktm1.1Rbar mutation (0 available); any Ctsk mutation (21 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Increase in cross-sectional bone volume and cortical bone volume in Ctsktm1.1Rbar/Ctsktm1.1Rbar Tg(Itgam-cre)AJva/0 femurs but not in Ctsktm1.1Rbar/Ctsktm1.1Rbar Tg(Mx1-cre)1Cgn/0 or Ctsktm1.1Rbar/Ctsktm1.1Rbar Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0 femurs

skeleton
N
• mice exhibit normal bone density




Genotype
MGI:5613581
cn42
Allelic
Composition
Gt(ROSA)26Sortm4(Wnt7b)Flng/Gt(ROSA)26Sor+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm4(Wnt7b)Flng mutation (0 available); any Gt(ROSA)26Sor mutation (745 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• at E16.5 display a much thicker bone collar and no bone marrow
• 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
• profoundly dense bones throughout the body at 2 months of age
• at E18.5 the marrow region is populated by mature osteoblasts
• 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
• slight delay in chondrocyte maturation at E14.5




Genotype
MGI:5689563
cn43
Allelic
Composition
Runx3tm3Yg/Runx3tm3Yg
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Runx3tm3Yg mutation (0 available); any Runx3 mutation (13 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• low survival rates

growth/size/body
• severe congenital dwarfism




Genotype
MGI:5586499
cx44
Allelic
Composition
Col1a1tm2(tetO-Fosl2,-DsRed)Wag/Col1a1+
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Col1a1tm2(tetO-Fosl2,-DsRed)Wag mutation (0 available); any Col1a1 mutation (141 available)
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular

skeleton
• decreased osteoclast surface
• increased osteoblast surface
• increased bone formation

homeostasis/metabolism
• in response to glucose stimulation
• in the pancreas
• 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
• 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
• 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
• 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

growth/size/body
• 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
• in response to glucose stimulation
• in the pancreas

adipose tissue
N
• mice exhibit normal adipocyte number and size
• 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
• decreased osteoclast surface

immune system
• decreased osteoclast surface




Genotype
MGI:5521546
cx45
Allelic
Composition
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Tg(tetO-RNAi:Trp53)ASlowe/0
Genetic
Background
involves: C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
Tg(tetO-RNAi:Trp53)ASlowe mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 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

mortality/aging
• median survival is 485 days of age

neoplasm
• 83.3% of mice show metastatic dissemination, commonly to the lung and liver
• 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
tg46
Allelic
Composition
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
Genetic
Background
involves: CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Sp7-tTA,tetO-EGFP/cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
limbs/digits/tail
• tibias are about 25% narrower at the mid-diaphysis compared to wild-type mice
• about 7% decrease in tibia length

skeleton
• tibias are about 25% narrower at the mid-diaphysis compared to wild-type mice
• about 7% decrease in tibia length
• trabecular bone volume in the metaphysis is reduced by about 36%, although this doesnt reach statistical significance
• cortical thickness is increased by about 14.5%





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
01/12/2022
MGI 6.17
The Jackson Laboratory