Tg(TG-Gnas*R201H)1Rho

The transgene contains nucleotides -2036 through +9 of the bovine thyroglobulin gene joined to a Chinese hamster cDNA encoding a mutant GNAS (guanine nucleotide binding protein, alpha stimulating) with arginine replaced by histidine at amino acid position 201 (R210H), followed by an intron and polyadenylation signal from the the SV40 small T antigen gene. Mutations at this position and at amino acid 227 are associated with thyroid toxic adenoma and thyroid carcinoma in humans. These mutations interfere with the GTPase activity of the alpha subunit, resulting in constitutive activation of the adenylate cyclase activity of guanine nucleotide stimulatory factor and elevated basal cAMP that is unaffected by thyroid stimulating hormone (TSH). Reverse transcription followed by polymerase chain reaction (RT-PCR) analysis with primers that distinguish transgene-derived from endogenous mouse Gnas transcripts reveals their coexpression in the thyroid glands of transgenic mice at 4 months of age, prior to the appearance of any histologic abnormalities, as well as in a visually apparent thyroid adenoma from a 12 month old mouse. The transgenic transcripts consistently are present at lower levels than the endogenous mRNAs, although at a relatively higher level in the adenoma. No transgene expression is detected in lung or thymus. (J:94546)