
<ArticleTitle>C-cell and thyroid epithelial tumours and altered follicular development in transgenic mice expressing the long isoform of <prot>MEN 2A RET</prot>.</ArticleTitle>
<AbstractText>Gain-of-function mutations in the gene encoding the receptor tyrosine kinase <prot>RET</prot> have been identified as the aetiological factor for multiple endocrine neoplasia type 2A (MEN2A). MEN2A is a dominantly-inherited cancer predisposition syndrome characterized by medullary thyroid carcinoma, a tumour of the calcitonin-producing thyroid C-cells. There are three isoforms of <prot>RET</prot>: <prot>RET9</prot>, <prot>RET43</prot> and <prot>RET51</prot>, and although in vitro evidence suggests they vary in cellular transformation activities, little is known about their function in tumorigenesis in vivo. To address this, we used <prot>RET51</prot> cDNA to construct mice in which the most frequent MEN2A mutation, Cys-634-Arg, was expressed under the control of the human <prot>calcitonin</prot> promoter (CT-2A mice). These mice developed C-cell tumours resembling human MTC and follicular tumours resembling human papillary thyroid carcinoma (PTC) depending on the founder line examined. One founder line developed compound MTC/PTC at low frequency (8%) and pancreatic cystadenocarcinoma. CT-2A mice also displayed a developmental defect in thyroid follicular structure, in which much of the thyroid was occupied by large irregular cystic follicles thought to be derived from the ultimobranchial body, a developmental precursor of the thyroid gland. The CT-2A mice will provide a suitable model to further study the effects of the <prot>MEN 2A RET</prot> mutation in vivo.</AbstractText>
