IMPC phenotypes (gene matching)
129S2(Cg)-Trp53tm2.1Thst/Orl
| Status | Available to order |
| EMMA ID | EM:13424 |
| International strain name | 129S2(Cg)-Trp53tm2.1Thst/Orl |
| Alternative name | 129S2-Trp53 |
| Strain type | Targeted Mutant Strains : Point mutation |
| Allele/Transgene symbol | Trp53tm2.1Thst |
| Gene/Transgene symbol | Trp53 |
Information from provider
| Provider | Thorsten Stiewe |
| Provider affiliation | Molecular Oncology Institute, Philipps University Marburg |
| Genetic information | The endogenous Trp53 allele carries a point mutation CGC->GAG in the exon 5 resulting in Arg->Glu substitution in the codon 178 |
| Phenotypic information | Homozygous:R178E substitution leads to severely compromised p53 DNA binding cooperativity, which results in loss of transcriptional activation of direct target genes and deficiency in p53-dependent transcription-mediated functions. Homozygous mice are resistant to gamma-irradiation induced apoptosis, are cancer-prone (tumor spectrum is very close to p53 knock-out - about 90% of tumors are T- and B-lymphoma) and have a strongly reduced lifespan (median overall survival of knock-ins 150 days, knock-outs 129 days, whereas the lifespan of the p53+/+ littermates exceeded 842 days).Heterozygous:Heterozygous p53+/R178E mice are tumor-prone and have reduced lifespan (median overall survival 519 days). The most frequent malignant tumors are sarcoma (47%), lymphoma (29%), and carcinoma (12%). |
| Breeding history | More than 20 backcrosses on 129S2/SvHsd background |
| References |
|
| Homozygous fertile | males only |
| 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 |
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
- Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.;Timofeev Oleg, Klimovich Boris, Schneikert Jean, Wanzel Michael, Pavlakis Evangelos, Noll Julia, Mutlu Samet, Elmshäuser Sabrina, Nist Andrea, Mernberger Marco, Lamp Boris, Wenig Ulrich, Brobeil Alexander, Gattenlöhner Stefan, Köhler Kernt, Stiewe Thorsten, ;2019;The EMBO journal;38;e102096; 31483066