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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
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 30% decrease in survival at 22 weeks of age

growth/size/body
• 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
• by 5 weeks of age
• 12- and 22-week old mice exhibit multifocal tumors involving both lobes of the thyroid gland and having mixed papillary and follicular growth pattern
• 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
• 12- and 22-week old mice exhibit multifocal tumors involving both lobes of the thyroid gland and having mixed papillary and follicular growth pattern
• 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
• 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
• 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

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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/12/2024
MGI 6.23
The Jackson Laboratory