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Title: Generation and analysis of an inducible thyroxine-deficient mouse model
Author: Wallace, Helen A. C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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The aim of this project was to create an inducible thyroxine-deficient mouse model which could be used to investigate the role of thyroxine in gene expression. This was achieved by using the HSV1-tk ablation technique. Transgenic mice were produced containing 3.1kb of the bovine thyroglobulin promoter linked to 1.8kb of the HSV1-tk gene. Expression of the transgene was detected in the thyroid and testes. Transcription of the transgene in transgenic thyroid tissue was correctly initiated at the cap site with 4.5mg/day of an anti-herpetic agent, such as ganciclovir, resulted in a deduction in the number of thyroid follicle cells within 3 days and their complete absence after 7 days. After 14 days of treatment the mice lacked circulating thyroid hormones, the HSV1-TK activity of the thyroid rudiments was comparable to non-transgenic controls and the total soluble protein remaining was approximately 20% of controls. The thyroid gland comprises two cell types, thryoxine producing thyrocytes and calcitonin producing C-cells. The gland is also in intimate contact with the parathyroid gland which secretes parathyroid hormone. The expression of the transgene was restricted to the thyroid follicle epithelial cells. Transgenic ablation resulted in the precise removal of HSV1-TK expressing cells with no secondary effect on either the C-cells or the parathyroid gland. My results also demonstrate that the normal function of the C-cells and parathyroid gland are not dependent on thyroid hormones. When treatment with ganciclovir was terminated no recovery of thyroid hormones in the circulation or HSV1-TK activity in the thyroid rudiment were observed (for up to 113 days). This suggests that young adult mice do not contain a non-differentiated stem cell that is capable of repopulating the follicle cells of the thyroid. The mouse major urinary proteins (MUP) genes in the liver are regulated by thyroid hormones and growth hormone. I investigated the role of thyroid hormones on the expression of resident MUP genes and also a MUP transgene and demonstrated that hepatic MUP gene expression is absolutely dependent on the presence of thyroid hormones.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available