ONCOGENIC POTENTIAL OF GUANINE-NUCLEOTIDE STIMULATORY FACTOR-ALPHA SUBUNIT IN THYROID-GLANDS OF TRANSGENIC MICE

Transgenic mice have been used to address the issue of the oncogenic p otential of mutant guanine nucleotide stimulatory factor (G(s)) alpha subunit in the thyroid gland. The expression of the mutant Arg-201 --> His G(s) alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter, The transgenic anim als develop hyperfunctioning thyroid adenomas with increased intracell ular cAMP levels and high uptake of [I-125]iodine and produced elevate d levels of circulating triiodothyronine and thyroxine. These animals demonstrate that the mutant form of G(s) alpha subunit carries an onco genic activity, thus supporting the model that deregulation of cAMP le vel alters growth control in thyroid epithelium. These animals represe nt models for humans with autonomously functioning thyroid nodules.