Phenotypes Associated with This Genotype

Genotype
MGI:2174782

• Allelic Composition: Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

premature death ( J:72391 , J:95318 )

• average life span 160 days (J:72391)

• homozygous mutants die between ~50 to 250 days after birth (J:95318)

decreased tumor-free survival time ( J:87501 )

• 90% succumb to tumors and die by 7 months of age

preweaning lethality, incomplete penetrance ( J:17728 )

• 16.6% rather than the expected 25% of mutants are observed at weaning, indicating partial lethality either during embryogenesis or after birth but before weaning

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:17728 , J:87501 )

• most lymphomas are thymic lymphomas (J:17728)

• 75% of observed tumors are thymic lymphomas (J:87501)

homeostasis/metabolism

abnormal iron homeostasis ( J:244082 )

• mouse embryonic fibroblasts (MEFs) show increased protein expression of IREB2 (iron responsive element binding protein 2; aka IRP2) and TFRC (transferrin receptor; aka TfR1) but reduced expression of ACO1 (aconitase 1; aka IRP1) and FTH1 (ferritin heavy polypeptide 1)

abnormal iron level ( J:244082 )

• Pearl's Prussian blue staining revealed mild iron overload in E8.0 embryos

• MEFs show mitochondrial iron accumulation

abnormal protein level ( J:244082 )

• MEFs show reduced protein levels of FDXR and CDKN1A (aka p21)

neoplasm

increased tumor incidence ( J:17728 , J:72391 )

• predominantly lymphomas with sarcomas and teratomas (J:17728)

increased hemangioma incidence ( J:72391 )

• 3.3% incidence

increased lymphoma incidence ( J:17728 , J:72391 , J:95318 )

• 71% of mice develop lymphoma, usually affecting the thymus (J:17728)

• 70% incidence (J:72391)

• 56% of homozygous nulls developed lymphomas (J:95318)

increased T cell derived lymphoma incidence ( J:17728 , J:87501 )

• most lymphomas are thymic lymphomas (J:17728)

• 75% of observed tumors are thymic lymphomas (J:87501)

increased carcinoma incidence ( J:72391 )

• 3.3% incidence

increased squamous cell carcinoma incidence ( J:72391 )

• 3.3% incidence of stomach squamous cell carcinoma

increased sarcoma incidence ( J:17728 , J:72391 , J:95318 )

• 50% incidence (J:72391)

• 40% of homozygous nulls developed sarcomas (J:95318)

increased rhabdomyosarcoma incidence ( J:17728 )

increased fibrosarcoma incidence ( J:72391 )

• 13% incidence

increased hemangiosarcoma incidence ( J:17728 , J:72391 )

• 20% incidence (J:72391)

increased osteosarcoma incidence ( J:17728 , J:72391 )

• 13% incidence (J:72391)

increased teratoma incidence ( J:17728 )

cellular

aneuploidy ( J:87501 )

abnormal mitochondrial morphology ( J:244082 )

• MEFs show mitochondrial iron accumulation

decreased cellular sensitivity to gamma-irradiation ( J:95318 )

• irradiated E13.5 heterozygous embryos showed no evidence of apoptosis in the hypothalamus compared to wildtype and heterozygotes that showed a high number of apoptotic cells

decreased cellular sensitivity to ultraviolet irradiation ( J:170976 )

• in mouse embryonic fibroblasts

abnormal apoptosis ( J:87501 )

increased fibroblast proliferation ( J:95318 )

• MEFs initially did not show any significant differences in growth rate but by day 4, grew more rapidly than wildtype or heterozygous MEFs

decreased cell proliferation ( J:170976 )

• in mouse embryonic fibroblasts treated with UV irradiation

muscle

increased rhabdomyosarcoma incidence ( J:17728 )

skeleton

increased osteosarcoma incidence ( J:17728 , J:72391 )

• 13% incidence (J:72391)

digestive/alimentary system

colon polyps ( J:72391 )

• 6.7% incidence

gastric polyps ( J:72391 )

• 3.3% incidence of stomach polyps