IMPC phenotypes (gene matching)
Trp53-R210X
| Status | Available to order |
| EMMA ID | EM:16205 |
| Citation information | RRID:IMSR_EM:16205 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information. |
| International strain name | Trp53-R210X |
| Alternative name | Trp53-R210X |
| Strain type | Endonuclease-mediated |
| Allele/Transgene symbol | Trp53em1Klgw |
| Gene/Transgene symbol | Trp53 |
Information from provider
| Provider | Klas Wiman |
| Provider affiliation | Oncology-Pathology, Karolinska Institutet |
| Genetic information | Trp53 nonsense mutation: p.R210X. CRISPR/Cas9 genome editing was used to introduce two single point mutations resulting in an Arg (CGC) to STOP (TGA) substitution at codon 210 in exon 6 of the Trp53 gene. The Trp53-R210X mouse model was generated using CRISPR/Cas9 genome editing to introduce two single point mutations resulting in an Arg (CGC) to STOP (TGA) substitution at codon 210 in exon 6 of the Trp53 gene. The edited mice were produced at the Karolinska Center for Transgene Technologies, Karolinska Institutet. Zygotes harvested from superovulated and mated C57BL/6J female mice (Charles River Laboratories, Germany) were microinjected into the pronuclei. Microinjected zygotes were implanted into oviducts of pseudo-pregnant SOPF RjOrl:SWISS (Janvier Labs, France) surrogate female mice via microsurgery. F0 offspring carrying the correct R210X mutation (genotyped by PCR and verified by Sanger sequencing) were set up for backcross breeding to WT C57BL/6J mice to eliminate possible off-target events. PCR genotyping of F1 offspring verified germline transmission of the R210X allele. Sequencing of 1049 bp surrounding the edited Trp53 exon 6 locus confirmed clean WT and R210X alleles in all F1 mice identified as heterozygous. The TP53 tumor suppressor gene is mutated in ca 50% of human tumors, and close to 11% of those TP53 mutations are nonsense mutations. The Trp53-R210X mouse model will be useful as a platform for development of novel strategies for therapeutic targeting of nonsense mutant TP53 in cancer. The Trp53-R210X mouse model is a model of the Li-Fraumeni Syndrome (inherited TP53 mutations). CRISPR technology details: eSpCas9 (Sigma-Aldrich/Merck, Germany) was used in the Cas9-sgRNA ribonucleoprotein complexes. |
| Phenotypic information | Homozygous:Initially, homozygous mice appear phenotypically normal, although the proportion of female homozygous mice is dramatically reduced. Female homozygous mice are poor breeders and remain smaller and lighter than female heterozygous and wildtype littermates. Homozygous mice start to show tumors at 2.5 months of age, and their maximal lifespan is 8.5 months. Homozygous mice develop hematopoietic and mesenchymal tumors, most commonly T-cell lymphoma (most frequently in the thymus) and leiomyosarcoma. About 2/3 of the homozyogous mice show multicentric or metastatic tumors (T-cell lymphomas, other hematopoietic tumors, and soft-tissue sarcomas). Heterozygous:Initially, heterozygous mice appear phenotypically normal. Heterozygous mice are good breeders. Heterozygous mice present tumors from 9 months of age, and by 16.5 months of age 50% of all heterozygous mice have developed overt tumors. Heterozygous mice develop hematopoietic, mesenchymal, epithelial and sex cord tumors, most commonly osteosarcoma and leiomyosarcoma. The majority of heterozygous mice with osteosarcomas are female. About 1/3 of the heterozygous mice show multicentric or metastatic tumors (hematopoietic, soft-tissue sarcomas, osteosarcomas, and carcinomas). 71% of tumors from heterozygous mice show loss of heterozygosity (LOH). |
| Breeding history | Trp53-R210X/+ F1 mice have been maintained on a C57BL/6J background by backcrossing to C57BL/6J mice purchased from Charles River Laboratories, currently F1N14 generation. |
| References |
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| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Karolinska Institutet, Stockholm, Sweden |
| Animals used for archiving | heterozygous C57BL/6J males |
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
- Mice carrying nonsense mutant p53 develop frequent multicentric or metastatic tumors.;Strandgren Charlotte, Rondahl Veronica, Oppelt Ann-Sophie, Öhlin Susanne, Heldin Angelos, Wiman Klas G, ;2025;Cell death & disease;17;85; 41381412