Analysis Tools
endocrine/exocrine glands
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• after 1 week exposure to doxycycline (dox), mutants show an 8-fold increase in thyroid mass, which regresses by 72 hours and reaches normal size by 7 weeks after dox withdrawal
• none of the mutants, however, develop thyroid abnormalities in the absence of doxycycline
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• after 1 week exposure to dox, all mutants develop thyroid cancer characterized by solid nests of tumor cells without follicular architecture or colloid formation
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• tumors of mutants exposed to dox exhibit nuclear enlargement, crowding and overlapping, irregularity of nuclear contours and occasional nuclear grooves, characteristics seen in human papillary thyroid carcinoma
• 3 of 8 mutants with poorly differentiated thyroid cancer show extrathyroidal extension of the tumor
• however, no lymph node or distant metastases are seen
• two weeks after dox withdrawal, thyroid glands of mutants are normal or have hyperplastic features and by 7 weeks off dox, all mice have normal thyroid histology
• an increase in apoptosis is seen within the center of the thyroid tumors within 72 hours of dox withdrawal and is no longer seen by 2 weeks
• treatment of dox induced thyroid tumors with PD0325901, a small molecule MEK inhibitor, or PLX4720 or PLX4032, selective inhibitors of BRAF, fails to induce tumor regression, although expression of thyroid-specific genes is partially restored and the BRAF inhibitors inhibit the proliferative index of tumors and renders tumor cells susceptible to radioiodine treatment
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• mutants become hypothyroid within 48 hours of dox administration, showing decreased serum T4 and thyrotrophin (TSH) levels
• removal of dox results in normalization of thyroid function
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homeostasis/metabolism
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• within 48 hours of dox administration, mutants show decreased serum T4 levels
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• within 48 hours of dox administration, mutants show decreased serum thyrotrophin levels
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neoplasm
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• after 1 week exposure to dox, all mutants develop thyroid cancer characterized by solid nests of tumor cells without follicular architecture or colloid formation
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• tumors of mutants exposed to dox exhibit nuclear enlargement, crowding and overlapping, irregularity of nuclear contours and occasional nuclear grooves, characteristics seen in human papillary thyroid carcinoma
• 3 of 8 mutants with poorly differentiated thyroid cancer show extrathyroidal extension of the tumor
• however, no lymph node or distant metastases are seen
• two weeks after dox withdrawal, thyroid glands of mutants are normal or have hyperplastic features and by 7 weeks off dox, all mice have normal thyroid histology
• an increase in apoptosis is seen within the center of the thyroid tumors within 72 hours of dox withdrawal and is no longer seen by 2 weeks
• treatment of dox induced thyroid tumors with PD0325901, a small molecule MEK inhibitor, or PLX4720 or PLX4032, selective inhibitors of BRAF, fails to induce tumor regression, although expression of thyroid-specific genes is partially restored and the BRAF inhibitors inhibit the proliferative index of tumors and renders tumor cells susceptible to radioiodine treatment
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| papillary thyroid carcinoma | DOID:3969 |
OMIM:188550 |
J:184420 | |
