Phenotypes Associated with This Genotype

Genotype
MGI:3582787

• Allelic Composition: Rb1^tm1Tyj/Rb1⁺; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

premature death ( J:19542 )

• the mean age of survival of double heterozygotes is slightly reduced relative to mice heterozygous for Rb1^tm1Tyj alone (9 months vs 11 months)

neoplasm

abnormal tumor morphology ( J:19542 )

• in nearly all double heterozygotes with pituitary and thyroid tumors, the wild-type allele of Rb1 is lost whereas the wild-type allele of Trp53 is retained

increased tumor incidence ( J:19542 )

• one of 7 individual double heterozygotes analyzed displayed a single pinealoblastoma (not detected in single heterozygotes); the wild-type alleles of both Rb1 and Trp53 were lost in this pineal tumor

increased pituitary melanotroph tumor incidence ( J:19542 )

• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe

increased thyroid tumor incidence ( J:19542 )

• ~75% of double heterozygous mice develop medullary thyroid tumors

increased pancreatic islet cell carcinoma incidence ( J:19542 )

• 14% of a total of 14 individual double heterozygotes analyzed displayed islet cell carcinomas (not detected in single heterozygotes)

• notably, the wild-type alleles of both Rb1 and Trp53 were lost in tumors of the islet cells of the pancreas

increased sarcoma incidence ( J:19542 )

• 6% of a total of 67 individual double heterozygotes analyzed displayed anaplastic sarcomas

• such tumors were shown to be more aggressive and arise at an earlier age than those occurring in single Trp53^tm1Tyj heterozygotes

• notably, the wild-type alleles of both Rb1 and Trp53 were lost in these anaplastic sarcomas

increased leiomyosarcoma incidence ( J:19542 )

• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma

respiratory system

bronchial epithelial hyperplasia ( J:19542 )

• 8% of a total of 12 individual double heterozygotes analyzed displayed bronchial hyperplasia

muscle

increased leiomyosarcoma incidence ( J:19542 )

• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma

endocrine/exocrine glands

increased pituitary melanotroph tumor incidence ( J:19542 )

• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe

increased thyroid tumor incidence ( J:19542 )

• ~75% of double heterozygous mice develop medullary thyroid tumors

increased pancreatic islet cell carcinoma incidence ( J:19542 )

• 14% of a total of 14 individual double heterozygotes analyzed displayed islet cell carcinomas (not detected in single heterozygotes)

• notably, the wild-type alleles of both Rb1 and Trp53 were lost in tumors of the islet cells of the pancreas

nervous system

increased pituitary melanotroph tumor incidence ( J:19542 )

• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe