Phenotypes Associated with This Genotype

Genotype
MGI:5779643

• Allelic Composition: Braf^tm1Cpri/Braf^tm1Cpri; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/NCr

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

growth/size/body

decreased body weight ( J:168249 )

• mice weigh about 50% less than wild-type littermates by weaning

homeostasis/metabolism

increased circulating thyroxine level ( J:168249 )

• by 5 weeks of age, serum T4 levels are decreased

increased circulating thyroid-stimulating hormone level ( J:168249 )

• by 5 weeks of age, serum TSH levels are about 500-fold greater than in wild-type mice

neoplasm

increased thyroid tumor incidence ( J:168249 )

• mice develop infiltrative papillary thyroid cancer with complete penetrance by 5 weeks of age

• tumors encompass the entire thyroid gland and have features of aggressive human papillary thyroid cancer with papillae lined by tall cells, with increased number of mitoses, nuclear clearing, and pseudonuclear inclusions

• administration of levothyroxine (L-T4) soon after birth for 3 weeks does not prevent the onset or alter the characteristics of papillary thyroid tumors

• administration of L-T4 for 3 weeks beginning at 5 weeks of age when all mice have tumors does not decrease the mitotic rate or alter the severity of the tumors

• mice treated with the MEK1/2 inhibitor PD325901 for 3 weeks beginning at 3 weeks of age exhibit a decrease in thyroid tumor volume and a modest reduction in proliferative index of tumors

increased thyroid carcinoma incidence ( J:168249 )

• tumor cells frequently invade perithyroidal tissues

• 66% of tumors invade into surrounding skeletal muscle by 5 weeks and vascular invasion is common

endocrine/exocrine glands

increased thyroid tumor incidence ( J:168249 )

• mice develop infiltrative papillary thyroid cancer with complete penetrance by 5 weeks of age

• tumors encompass the entire thyroid gland and have features of aggressive human papillary thyroid cancer with papillae lined by tall cells, with increased number of mitoses, nuclear clearing, and pseudonuclear inclusions

• administration of levothyroxine (L-T4) soon after birth for 3 weeks does not prevent the onset or alter the characteristics of papillary thyroid tumors

• administration of L-T4 for 3 weeks beginning at 5 weeks of age when all mice have tumors does not decrease the mitotic rate or alter the severity of the tumors

• mice treated with the MEK1/2 inhibitor PD325901 for 3 weeks beginning at 3 weeks of age exhibit a decrease in thyroid tumor volume and a modest reduction in proliferative index of tumors

increased thyroid carcinoma incidence ( J:168249 )

• tumor cells frequently invade perithyroidal tissues

• 66% of tumors invade into surrounding skeletal muscle by 5 weeks and vascular invasion is common

decreased activity of thyroid gland ( J:168249 )

• mice are euthyroid at P3, however by 5 weeks of age, mice are hypothyroid

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
papillary thyroid carcinoma		DOID:3969	OMIM:188550	J:168249