Phenotypes associated with this allele

• Allele Symbol: Tg(TPO-cre/ERT2)1139Tyj
• Allele Name: transgene insertion 1139, Tyler Jacks
• Allele ID: MGI:5565332
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Braf^tm1Mmcm/Braf^+ Tg(TPO-cre/ERT2)1139Tyj/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac	MGI:5897855
cn2	Braf^tm1Mmcm/Braf^+ Trp53^tm3.1Tyj/Trp53^+ Tg(TPO-cre/ERT2)1139Tyj/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac	MGI:5897857
cn3	Braf^tm1Mmcm/Braf^+ Trp53^tm1Brn/Trp53^tm3.1Tyj Tg(TPO-cre/ERT2)1139Tyj/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac	MGI:5897858
cn4	Braf^tm1Mmcm/Braf^+ Tg(TPO-cre/ERT2)1139Tyj/0 Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac	MGI:5897859

Genotype
MGI:5897855

cn1

• Allelic Composition: Braf^tm1Mmcm/Braf⁺; Tg(TPO-cre/ERT2)1139Tyj/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac

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

endocrine/exocrine glands

increased thyroid carcinoma incidence ( J:208854 )

• mice administered tamoxifen develop papillary thyroid carcinomas

• tumors show both papillary growth morphology and nuclear features of papillary thyroid carcinoma

• even with very long latency, extrathyroidal invasion is not seen and cervical lymph node metastases are not seen

neoplasm

increased thyroid carcinoma incidence ( J:208854 )

• mice administered tamoxifen develop papillary thyroid carcinomas

• tumors show both papillary growth morphology and nuclear features of papillary thyroid carcinoma

• even with very long latency, extrathyroidal invasion is not seen and cervical lymph node metastases are not seen

respiratory system

respiratory failure ( J:208854 )

• tamoxifen treated mice generally succumb to respiratory compromise due to tracheal compression by large noninvasive tumors

Genotype
MGI:5897857

cn2

• Allelic Composition: Braf^tm1Mmcm/Braf⁺; Trp53^tm3.1Tyj/Trp53⁺; Tg(TPO-cre/ERT2)1139Tyj/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac

mortality/aging

premature death ( J:208854 )

• tamoxifen treated mice exhibit shortened survival

endocrine/exocrine glands

increased thyroid carcinoma incidence ( J:208854 )

• tamoxifen treated mice develop large papillary thyroid carcinoma that exhibit features associated with aggressive behavior including solid growth, tall cell morphology, focal necrosis, and hobnail features

• about 50% of mice with papillary thyroid carcinoma acquire poorly differentiated thyroid carcinoma or undifferentiated anaplastic thyroid carcinoma

neoplasm

increased thyroid carcinoma incidence ( J:208854 )

• tamoxifen treated mice develop large papillary thyroid carcinoma that exhibit features associated with aggressive behavior including solid growth, tall cell morphology, focal necrosis, and hobnail features

• about 50% of mice with papillary thyroid carcinoma acquire poorly differentiated thyroid carcinoma or undifferentiated anaplastic thyroid carcinoma

Genotype
MGI:5897858

cn3

• Allelic Composition: Braf^tm1Mmcm/Braf⁺; Trp53^tm1Brn/Trp53^tm3.1Tyj; Tg(TPO-cre/ERT2)1139Tyj/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac

endocrine/exocrine glands

increased thyroid carcinoma incidence ( J:208854 )

• tamoxifen treated mice exhibit accelerated progression to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis

neoplasm

increased thyroid carcinoma incidence ( J:208854 )

• tamoxifen treated mice exhibit accelerated progression to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis

Genotype
MGI:5897859

cn4

• Allelic Composition: Braf^tm1Mmcm/Braf⁺; Tg(TPO-cre/ERT2)1139Tyj/0; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * C57BL/6NTac

mortality/aging

decreased tumor-free survival time ( J:208854 )

• median survival of about 6 months following tumor induction with tamoxifen

• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival

• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901show prolonged survival

neoplasm

increased thyroid carcinoma incidence ( J:208854 )

• tamoxifen treated mice exhibit accelerated progression from papillary thyroid carcinoma to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis

• carcinoma in tamoxifen treated mice shows tracheal invasion and extrathyroidal extension

• marker analysis indicates that anaplastic thyroid carcinoma in tamoxifen treated mice originates from thyroid epithelium

• tumors from tamoxifen treated mice exhibit very slow initial growth upon induction but rapid tumor growth after a variable latency

• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels and develop anaplastic thyroid carcinoma with a similar latency as unsupplemented controls

• anaplastic thyroid carcinomas exhibit a gene expression profile of high-grade, undifferentiated carcinomas

• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival and a decrease in contralateral papillary thyroid carcinomas, however no decrease in anaplastic thyroid carcinoma size is seen and tumors even grow larger

• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901 show complete regression of tumors and prolonged survival

increased metastatic potential ( J:208854 )

• 19% of tamoxifen treated mice exhibit lung metastases

• however, region lymph node metastases are not seen

endocrine/exocrine glands

increased thyroid carcinoma incidence ( J:208854 )

• tamoxifen treated mice exhibit accelerated progression from papillary thyroid carcinoma to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis

• carcinoma in tamoxifen treated mice shows tracheal invasion and extrathyroidal extension

• marker analysis indicates that anaplastic thyroid carcinoma in tamoxifen treated mice originates from thyroid epithelium

• tumors from tamoxifen treated mice exhibit very slow initial growth upon induction but rapid tumor growth after a variable latency

• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels and develop anaplastic thyroid carcinoma with a similar latency as unsupplemented controls

• anaplastic thyroid carcinomas exhibit a gene expression profile of high-grade, undifferentiated carcinomas

• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival and a decrease in contralateral papillary thyroid carcinomas, however no decrease in anaplastic thyroid carcinoma size is seen and tumors even grow larger

• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901 show complete regression of tumors and prolonged survival

homeostasis/metabolism

increased thyroid-stimulating hormone level ( J:208854 )

• small increase in TSH levels (less than 10-fold elevation) in tamoxifen treated mice

• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels

respiratory system

respiratory failure ( J:208854 )

• tamoxifen treated mice quickly deteriorate after progression to anaplastic thyroid carcinoma, with rapidly growing neck masses and development of audible respiratory stridor