IMPC phenotypes (gene matching)
129S2(Cg)-Trp53tm1.1Thst/Orl
| Status | Available to order |
| EMMA ID | EM:13422 |
| International strain name | 129S2(Cg)-Trp53tm1.1Thst/Orl |
| Alternative name | 129S2-Trp53 tm1.1Thst/ Thst |
| Strain type | Targeted Mutant Strains : Point mutation |
| Allele/Transgene symbol | Trp53tm1.1Thst |
| Gene/Transgene symbol | Trp53 |
Information from provider
| Provider | Thorsten Stiewe |
| Provider affiliation | Institute of Molecular Oncology, Philipps University Marburg |
| Genetic information | The endogenous Trp53 allele, carries a point mutation, GAG to CGG in exon 5, resulting in Glu to Arg substitution at codon 177. |
| Phenotypic information | Homozygous:E177R substitution leads to reduced p53 DNA binding cooperativity, which results in decreased transcriptional activation of target genes and deficiency in p53-dependent transcription-mediated apoptosis. Homozygous mice are resistant to gamma-irradiation induced apoptosis, are cancer-prone (B-cell and T-cell lymphoma, angiosarcoma, carcinoma; 21% develop spleen hyperplasia) and have a reduced lifespan (median overall survival of 361 days, whereas the lifespan of the p53+/+ littermates exceeded 770 days).Heterozygous:Heterozygous p53+/E177R mice are tumor-prone and have reduced lifespan (median overall survival 587 days). Among all neoplasms detected in heterozygous mice the frequency of non-malignant tumors (predominantly spleen hyperplasia) reaches 50%, malignant tumors are represented by B-cell lymphoma, sarcoma/angiosarcoma and carcinoma. |
| Breeding history | More than 20 backcrosses to 129S2/SvHsd background. |
| References |
|
| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Institut de Transgenose, INTRAGENE, Orléans, France |
| Animals used for archiving | heterozygous 129S/SvHsd, wild-type 129S/SvHsd |
| Stage of embryos | 2-cell |
Disease and phenotype information
MGI phenotypes (gene matching)
- decreased bone mineral density / MGI
- osteopetrosis / MGI
- kyphosis / MGI
- lordosis / MGI
- decreased hematocrit / MGI
- decreased leukocyte cell number / MGI
- decreased neutrophil cell number / MGI
- extramedullary hematopoiesis / MGI
- enlarged heart / MGI
- abnormal cell death / MGI
- decreased bone marrow cell number / MGI
- altered response to myocardial infarction / MGI
- abnormal cell proliferation / MGI
- increased cell proliferation / MGI
- decreased cell proliferation / MGI
- abnormal coat/ hair morphology / MGI
- sparse hair / MGI
- delayed hair regrowth / MGI
- intestinal ulcer / MGI
- abnormal tibia morphology / MGI
- abnormal digit pigmentation / MGI
- increased foot pad pigmentation / MGI
- kinked tail / MGI
- enlarged liver / MGI
- liver hypoplasia / MGI
- abnormal mammary gland development / MGI
- abnormal spleen morphology / MGI
- enlarged spleen / MGI
- small spleen / MGI
- spleen hyperplasia / MGI
- spleen hypoplasia / MGI
- abnormal Peyer's patch morphology / MGI
- abnormal thymus morphology / MGI
- small thymus / MGI
- abnormal tongue morphology / MGI
- decreased brain size / MGI
- cerebellum hypoplasia / MGI
- abnormal cerebellar foliation / MGI
- absent cerebellum vermis / MGI
- abnormal cerebellar Purkinje cell layer / MGI
- exencephaly / MGI
- small gonad / MGI
- small testis / MGI
- abnormal spermatogenesis / MGI
- decreased sensitivity to skin irradiation / MGI
- skin lesions / MGI
- thin dermal layer / MGI
- decreased body weight / MGI
- weight loss / MGI
- decreased body size / MGI
- increased metastatic potential / MGI
- abnormal retina morphology / MGI
- abnormal optic nerve morphology / MGI
- absent optic nerve / MGI
- ataxia / MGI
- abnormal cardiovascular system physiology / MGI
- abnormal hematopoietic system physiology / MGI
- anemia / MGI
- cardiac hypertrophy / MGI
- abnormal apoptosis / MGI
- increased mortality induced by gamma-irradiation / MGI
- postnatal growth retardation / MGI
- increased inflammatory response / MGI
- liver inflammation / MGI
- lung inflammation / MGI
- vasculitis / MGI
- increased mammary adenocarcinoma incidence / MGI
- hemorrhage / MGI
- testis hypoplasia / MGI
- neoplasm / MGI
- abnormal tumor incidence / MGI
- increased tumor incidence / MGI
- increased B cell derived lymphoma incidence / MGI
- increased T cell derived lymphoma incidence / MGI
- increased leukemia incidence / MGI
- increased lung adenocarcinoma incidence / MGI
- increased sarcoma incidence / MGI
- increased leiomyosarcoma incidence / MGI
- increased rhabdomyosarcoma incidence / MGI
- increased carcinoma incidence / MGI
- increased lung adenoma incidence / MGI
- increased skin papilloma incidence / MGI
- decreased tumor incidence / MGI
- premature death / MGI
- abnormal limb morphology / MGI
- abnormal definitive hematopoiesis / MGI
- no abnormal phenotype detected / MGI
- muscular atrophy / MGI
- abnormal spleen white pulp morphology / MGI
- abnormal spleen marginal zone morphology / MGI
- increased intestinal adenoma incidence / MGI
- abnormal megakaryocyte progenitor cell morphology / MGI
- abnormal lymphocyte morphology / MGI
- increased teratoma incidence / MGI
- hepatic steatosis / MGI
- opacity of vitreous body / MGI
- abnormal retinal vasculature morphology / MGI
- increased heart weight / MGI
- abnormal ocular fundus morphology / MGI
- decreased erythrocyte cell number / MGI
- delayed wound healing / MGI
- increased hemangioma incidence / MGI
- decreased mortality induced by ionizing radiation / MGI
- no phenotypic analysis / MGI
- liver cirrhosis / MGI
- abnormal cell cycle / MGI
- abnormal telomere length / MGI
- thrombocytopenia / MGI
- decreased neuron apoptosis / MGI
- decreased cellular sensitivity to gamma-irradiation / MGI
- colon polyps / MGI
- gastric polyps / MGI
- increased hepatocellular carcinoma incidence / MGI
- decreased liver weight / MGI
- renal hypoplasia / MGI
- decreased tumor growth/size / MGI
- abnormal tumor morphology / MGI
- increased hemangiosarcoma incidence / MGI
- oxidative stress / MGI
- pallor / MGI
- oral leukoplakia / MGI
- abnormal thymus physiology / MGI
- premature aging / MGI
- increased osteosarcoma incidence / MGI
- decreased kidney weight / MGI
- enhanced cellular glucose import / MGI
- increased mortality induced by ionizing radiation / MGI
- abnormal chromosome number / MGI
- aneuploidy / MGI
- polyploidy / MGI
- spontaneous chromosome breakage / MGI
- abnormal cell cycle checkpoint function / MGI
- abnormal cerebellar cortex morphology / MGI
- abnormal spine curvature / MGI
- increased squamous cell carcinoma incidence / MGI
- increased cellular sensitivity to ionizing radiation / MGI
- decreased cellular sensitivity to ionizing radiation / MGI
- increased testicular teratoma incidence / MGI
- increased incidence of tumors by chemical induction / MGI
- increased incidence of tumors by ionizing radiation induction / MGI
- decreased incidence of tumors by chemical induction / MGI
- decreased circulating insulin-like growth factor I level / MGI
- increased hematopoietic stem cell number / MGI
- decreased hematopoietic stem cell number / MGI
- decreased skeletal muscle mass / MGI
- decreased testis weight / MGI
- decreased spleen weight / MGI
- decreased neuronal precursor cell number / MGI
- decreased T cell proliferation / MGI
- liver hyperplasia / MGI
- pancytopenia / MGI
- abnormal posterior eye segment morphology / MGI
- lethargy / MGI
- increased brain size / MGI
- growth/size/body region phenotype / MGI
- cellular phenotype / MGI
- immune system phenotype / MGI
- reproductive system phenotype / MGI
- darkened coat color / MGI
- increased angiogenesis / MGI
- abnormal cell physiology / MGI
- decreased apoptosis / MGI
- pulmonary fibrosis / MGI
- thin cerebellar granule layer / MGI
- optic nerve degeneration / MGI
- optic nerve hypoplasia / MGI
- increased medulloblastoma incidence / MGI
- abnormal mesenchyme morphology / MGI
- abnormal common myeloid progenitor cell morphology / MGI
- decreased T cell apoptosis / MGI
- increased ovary tumor incidence / MGI
- delayed cellular replicative senescence / MGI
- intestine polyps / MGI
- increased liver tumor incidence / MGI
- abnormal DNA replication / MGI
- increased pro-B cell number / MGI
- abnormal male germ cell apoptosis / MGI
- increased cellular sensitivity to ultraviolet irradiation / MGI
- decreased cellular sensitivity to ultraviolet irradiation / MGI
- decreased spleen red pulp amount / MGI
- increased circulating tumor necrosis factor level / MGI
- increased circulating interferon-gamma level / MGI
- increased circulating interleukin-6 level / MGI
- increased circulating interleukin-3 level / MGI
- increased circulating interleukin-5 level / MGI
- decreased survivor rate / MGI
- decreased common myeloid progenitor cell number / MGI
- decreased subcutaneous adipose tissue amount / MGI
- chromosomal instability / MGI
- abnormal physiological response to xenobiotic / MGI
- abnormal enterocyte apoptosis / MGI
- increased enterocyte apoptosis / MGI
- increased sensitivity to induced cell death / MGI
- decreased sensitivity to induced cell death / MGI
- decreased erythroid progenitor cell number / MGI
- increased pancreas tumor incidence / MGI
- abnormal thymocyte apoptosis / MGI
- increased brain tumor incidence / MGI
- increased adenocarcinoma incidence / MGI
- increased follicular lymphoma incidence / MGI
- increased splenic marginal zone lymphoma incidence / MGI
- increased histiocytic sarcoma incidence / MGI
- increased splenocyte proliferation / MGI
- decreased splenocyte apoptosis / MGI
- increased thymocyte apoptosis / MGI
- decreased thymocyte apoptosis / MGI
- abnormal abdominal lymph node morphology / MGI
- decreased sensitivity to induced morbidity/mortality / MGI
- increased sensitivity to xenobiotic induced morbidity/mortality / MGI
- increased tumor latency / MGI
- abnormal neuron differentiation / MGI
- increased reproductive system tumor incidence / MGI
- increased urinary system tumor incidence / MGI
- increased skin tumor incidence / MGI
- increased hamartoma incidence / MGI
- abnormal tumor latency / MGI
- decreased tumor latency / MGI
- increased lipoma incidence / MGI
- increased hibernoma incidence / MGI
- increased teratocarcinoma incidence / MGI
- increased fibrosarcoma incidence / MGI
- increased spindle cell carcinoma incidence / MGI
- increased adenoma incidence / MGI
- abnormal hematopoietic stem cell physiology / MGI
- mortality/aging / MGI
- postnatal lethality, complete penetrance / MGI
- postnatal lethality, incomplete penetrance / MGI
- embryonic lethality during organogenesis, complete penetrance / MGI
- preweaning lethality, complete penetrance / MGI
- prenatal lethality, incomplete penetrance / MGI
- embryonic lethality during organogenesis, incomplete penetrance / MGI
- lethality throughout fetal growth and development, incomplete penetrance / MGI
- preweaning lethality, incomplete penetrance / MGI
- increased tail pigmentation / MGI
- increased fibroblast proliferation / MGI
- decreased hematopoietic stem cell proliferation / MGI
- nail dystrophy / MGI
- increased lymphoma incidence / MGI
- abnormal tail tip morphology / MGI
- decreased fibroblast apoptosis / MGI
- adipose tissue inflammation / MGI
Literature references
- Inactivation of Mdm2 restores apoptosis proficiency of cooperativity mutant p53 in vivo.;Klimovich Boris, Stiewe Thorsten, Timofeev Oleg, ;2020;Cell cycle (Georgetown, Tex.);19;109-123; 31749402
- p53 DNA binding cooperativity is essential for apoptosis and tumor suppression in vivo.;Timofeev Oleg, Schlereth Katharina, Wanzel Michael, Braun Attila, Nieswandt Bernhard, Pagenstecher Axel, Rosenwald Andreas, Elsässer Hans-Peter, Stiewe Thorsten, ;2013;Cell reports;3;1512-25; 23665223