MUTATIONAL ANALYSIS OF THE THYROTROPIN RECEPTOR GENE IN SPORADIC AND FAMILIAL FELINE THYROTOXICOSIS

The characterization of a spontaneous animal model equivalent to a hum an form of thyrotoxicosis would provide a useful resource for the inve stigation of the human disorder. Feline thyrotoxicosis is the only com mon form of hyperthyroidism found in domestic or laboratory animals, b ut its etiopathogenesis remains poorly defined. We have used the polym erase chain reaction (PCR) to amplify codons 480-640 of the previously uncharacterized feline thyrotropin receptor (TSHR) gene, and have det ermined the DNA sequence in this transmembrane domain region. We have analyzed single stranded conformational polymorphisms in thyroid DNA f rom 11 sporadic cases of feline thyrotoxicosis and leukocyte DNA from two cases of familial feline thyrotoxicosis. We have also determined t he DNA sequence of this region of the TSHR in five of the cases of spo radic feline thyrotoxicosis and the two familial thyrotoxic cats. The normal feline TSHR sequence between codons 480-640 is highly homologou s to that of other mammalian TSHRs, with 95%, 92%, and 90% amino acid identity between the feline receptor and canine, human, and bovine TSH Rs, respectively. Thyroid gland DNA from 11 cats with sporadic thyroto xicosis did not have mutations in this region of the TSHR gene. Leukoc yte DNA from two littermates with familial feline thyrotoxicosis did n ot harbor mutations of this region of the TSHR gene. These studies sug gest that TSHR gene mutations are not a common cause of feline thyroto xicosis.