Specific ablation of thyroid follicle cells in adult transgenic mice.
The coding region of the herpes simplex type 1 virus thymidine kinase gene was coupled to the promoter of the bovine thyroglobulin gene and introduced into the genome of mice. The viral thymidine kinase (HSV1-TK) was expressed mainly in the thyroid glands and testis. Upon treatment of transgenic females with the antiherpetic agent Ganciclovir the thyroid regressed, while the parathyroid gland was unaffected. The number of thyroid follicle cells was greatly reduced after 3 days, and they were completely absent after 7 days of treatment. After 14 days, the levels of circulating T4 and T3 were below the limits of detection, total soluble protein recovered from the thyroid and parathyroid glands together was 10% of the control value, and the level of thyroid HSV1-TK was more than 100-fold lower than that in transgenic controls. Levels of circulating PTH and calcitonin remained normal. At the time of treatment the mice were adults. Thus, the thyroid follicle cells were selectively ablated after normal development with a functional thyroid gland. When treatment with Ganciclovir was terminated after 14 days, no circulating T4 or T3 or other indications of thyroid regeneration were detected for a subsequent period of 90 days. During this time the mice gained weight more slowly than controls, at a rate consistent with the suppression of GH synthesis by thyroid deficiency. The production of mouse major urinary protein (MUP) ceased in the treated mice and was completely restored by the administration of T4. MUP production was not restored by GH, demonstrating that the expression of the Mup genes requires T4 in addition to GH.
Wallace
H
H
Institute of Cell and Population Biology, University of Edinburgh, United Kingdom.
Ledent
C
C
Vassart
G
G
Bishop
J O
JO
al-Shawi
R
R
D000818:Animals; D001483:Base Sequence; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D005818:Genetic Engineering; D007037:Hypothyroidism / Q000097:blood / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013974:Thyroxine / Q000097:blood; D014162:Transfection; D014284:Triiodothyronine / Q000097:blood
D011506:Proteins; C035737:major urinary proteins; D014284:Triiodothyronine; D013954:Thyroglobulin; D013937:Thymidine Kinase; D015774:Ganciclovir; D013974:Thyroxine