Phenotypes Associated with This Genotype

Genotype
MGI:5780077

• Allelic Composition: Braf^tm1Mmcm/Braf⁺; Tg(Tg-cre/ERT2)#Mmcm/0
• Genetic Background: involves: 129P2/OlaHsd

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

neoplasm

increased thyroid carcinoma incidence ( J:172205 )

• mice develop extensive papillary thyroid carcinomas by 12 months of tamoxifen treatment, first showing enlarged follicles within 7 days of tamoxifen treatment, a squamous morphology of thyrocytes accompanied by a large increase in follicle size and loss of colloid by 14 days of tamoixfen treatment, and tumor cells with characteristic papillary structure by 6 months of tamoxifen administration

• occasionally localized tumor invasion into the surrounding muscle is seen, however frank metastasis to lymph nodes or distant organs is not observed

• although mice have palpable thyroid tumors by 13 months of tamoxifen treatment, mice are not overtly sick

• mice not treated with tamoxifen show regions of papillary thyroid cancer with adjacent histologically normal thyroid architecture at 12 months of age, however these mice exhibit normal TSH and T4 levels

• treatment with PD0325901, an MEK1/2 inhibitor, results in regression of papillary thyroid cancer in tamoxifen-administered mutants

• treatment with PD0325901 and T3 results in further papillary thyroid cancer regression in tamoxifen-administered mutants

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:172205 )

• mice not treated with tamoxifen exhibit increased thyroid volume, however thyroid architecture is normal, indicating some leakiness of the cre transgene

abnormal thyroid follicle morphology ( J:172205 )

• within 7 days of tamoxifen treatment, mice show enlarged follicles throughout the entire gland

enlarged thyroid gland ( J:172205 )

• tamoxifen treated mice develop an enlarged, goiterous, hypercellular thyroid that is up to 10 times larger than controls at 1 month and up to 300 times larger at 12 months after tamoxifen treatment

• treatment with PD0325901 leads to decreased thyroid size of tamoxifen-administered mice

increased thyroid carcinoma incidence ( J:172205 )

• mice develop extensive papillary thyroid carcinomas by 12 months of tamoxifen treatment, first showing enlarged follicles within 7 days of tamoxifen treatment, a squamous morphology of thyrocytes accompanied by a large increase in follicle size and loss of colloid by 14 days of tamoixfen treatment, and tumor cells with characteristic papillary structure by 6 months of tamoxifen administration

• occasionally localized tumor invasion into the surrounding muscle is seen, however frank metastasis to lymph nodes or distant organs is not observed

• although mice have palpable thyroid tumors by 13 months of tamoxifen treatment, mice are not overtly sick

• mice not treated with tamoxifen show regions of papillary thyroid cancer with adjacent histologically normal thyroid architecture at 12 months of age, however these mice exhibit normal TSH and T4 levels

• treatment with PD0325901, an MEK1/2 inhibitor, results in regression of papillary thyroid cancer in tamoxifen-administered mutants

• treatment with PD0325901 and T3 results in further papillary thyroid cancer regression in tamoxifen-administered mutants

decreased activity of thyroid gland ( J:172205 )

• mice develop hypothyroidism by 1-3 months of tamoxifen treatment

homeostasis/metabolism

increased circulating thyroid-stimulating hormone level ( J:172205 )

• 100-fold increase in serum TSH levels at 1 and 3 months of tamoxifen treatment

• mice not treated with tamoxifen exhibit normal levels of TSH

decreased circulating thyroxine level ( J:172205 )

• mice exhibit a decrease in serum T4 levels at 1 and 3 months of tamoxifen treatment

• mice not treated with tamoxifen exhibit normal T4 levels

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid gland papillary carcinoma		DOID:3969	OMIM:188550	J:172205