Phenotypes Associated with This Genotype

Genotype
MGI:5897837

• Allelic Composition: Pten^tm2.1Ppp/Pten^tm2.1Ppp; Trp53^tm1Brn/Trp53^tm1Brn; Tg(TPO-cre)1Shk/0
• Genetic Background: 129.Cg-Tg(TPO-cre)1Shk Trp53^tm1Brn Pten^tm2.1Ppp

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

mortality/aging

premature death ( J:211100 )

• median survival is 38.4 weeks

neoplasm

increased thyroid carcinoma incidence ( J:211100 )

• 4-8 week old mice only show areas of well differentiated follicular carcinomas but go on to develop well-differentiated follicular carcinomas by 8-10 months of age exhibiting spindle cell morphology, giant, osteoclast-like, multinucleated cells and areas of osseous metaplasia resembling human thyroid anaplastic carcinomas

• anaplastic thyroid carcinomas undergo dedifferentiation, genomic instability and epithelial-to-mesenchymal transition and exhibit a shift from an oxidative to a glycolytic pathway

increased metastatic potential ( J:211100 )

• aggressive tumors invade locally into the muscle and trachea and metastasize to the lungs in 28% of mice, or less often, to the liver

endocrine/exocrine glands

enlarged thyroid gland ( J:211100 )

• all 8-10 month old mice exhibit enlarged thyroid gland causing severe tracheal compression

increased thyroid carcinoma incidence ( J:211100 )

• 4-8 week old mice only show areas of well differentiated follicular carcinomas but go on to develop well-differentiated follicular carcinomas by 8-10 months of age exhibiting spindle cell morphology, giant, osteoclast-like, multinucleated cells and areas of osseous metaplasia resembling human thyroid anaplastic carcinomas

• anaplastic thyroid carcinomas undergo dedifferentiation, genomic instability and epithelial-to-mesenchymal transition and exhibit a shift from an oxidative to a glycolytic pathway

homeostasis/metabolism

decreased thyroid-stimulating hormone level ( J:211100 )

• reduction in TSH serum levels

• however, T4 levels are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid gland carcinoma		DOID:3963		J:211100