Phenotypes Associated with This Genotype

Genotype
MGI:5524236

• Allelic Composition: Tg(TG-BRAF*V600E)2Jaf/0
• Genetic Background: FVB/N-Tg(TG-BRAF*V600E)2Jaf

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

mortality/aging

premature death ( J:98550 )

• 30% decrease in survival at 22 weeks of age

growth/size/body

slow postnatal weight gain ( J:98550 )

• mutants initially grow slightly slower than controls but by 8 weeks of age, no differences are seen; this lower body weight is more pronounced in males than females

endocrine/exocrine glands

enlarged thyroid gland ( J:98550 )

• by 5 weeks of age

increased thyroid tumor incidence ( J:98550 )

• 12- and 22-week old mice exhibit multifocal tumors involving both lobes of the thyroid gland and having mixed papillary and follicular growth pattern

increased thyroid carcinoma incidence ( J:98550 )

• tumor cells show nuclear features characteristic of human papillary carcinoma, including nuclear enlargement, overlapping and crowding, irregular nuclear contours, and occasional chromatin clearing and nuclear grooves

• almost all tumors have focal areas showing well-defined tall-cell features

• about 50% of 12- and 22-week old mice show focal areas of dedifferentiation composed of solid sheets of spindle cells lacking characteristic nuclear features of papillary carcinoma and showing no evidence of follicular architecture or colloid formation with microscopic appearance similar to human poorly differentiated carcinoma

• however, no severe nuclear atypia or tumor necrosis that are characteristic of human anaplastic (undifferentiated) carcinoma are seen

• frequency of dedifferentiation and vascular invasion are higher in males than in females

• tumors show aggressive malignancy and frequently invade blood vessels and thyroid gland capsule with extrathyroidal extension into adjacent adipose tissue and skeletal muscle

neoplasm

increased thyroid tumor incidence ( J:98550 )

• 12- and 22-week old mice exhibit multifocal tumors involving both lobes of the thyroid gland and having mixed papillary and follicular growth pattern

increased thyroid carcinoma incidence ( J:98550 )

• tumor cells show nuclear features characteristic of human papillary carcinoma, including nuclear enlargement, overlapping and crowding, irregular nuclear contours, and occasional chromatin clearing and nuclear grooves

• almost all tumors have focal areas showing well-defined tall-cell features

• about 50% of 12- and 22-week old mice show focal areas of dedifferentiation composed of solid sheets of spindle cells lacking characteristic nuclear features of papillary carcinoma and showing no evidence of follicular architecture or colloid formation with microscopic appearance similar to human poorly differentiated carcinoma

• however, no severe nuclear atypia or tumor necrosis that are characteristic of human anaplastic (undifferentiated) carcinoma are seen

• frequency of dedifferentiation and vascular invasion are higher in males than in females

• tumors show aggressive malignancy and frequently invade blood vessels and thyroid gland capsule with extrathyroidal extension into adjacent adipose tissue and skeletal muscle

homeostasis/metabolism

decreased circulating triiodothyronine level ( J:98550 )

• serum total triiodothyronine levels tend to be lower at all time points in both males and females, but are statistically significant only in 8 week old males

increased circulating thyroid-stimulating hormone level ( J:98550 )

• thyroid-stimulating hormone (TSH) levels in males are on average 80-fold greater than in wild-type mice at 5 weeks of age

• TSH levels in females are 5- to 8-fold increased and do not vary with time

• TSH levels decline at 8-12 weeks of age, but they are still elevated compared to wild-type mice

• however, serum total thyroxine and free thyroxine levels are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
papillary thyroid carcinoma		DOID:3969	OMIM:188550	J:98550 , J:195921