 The RET/PTC oncogene, a rearranged form of the RET proto-oncogene, has been found to be associated with human papillary thyroid carcinomas.     ///    "To investigate whether RET/PTC causes papillary thyroid carcinoma, we generated a transgenic mouse model of papillary thyroid carcinoma with targeted expression of RET/PTC1 in the thyroid gland. "    ///    The time of tumor onset appears to be dependent on the expression level of RET/PTC1 in these transgenic mice.     ///    "Finally, in order to investigate whether tumors induced by RET/PTC3 are more aggressive than those tumors induced by RET/PTC1, we also generated thyroid-targeted RET/PTC3 transgenic mice.. "    ///    This finding suggests that signaling pathways mediated by one or more of these three phosphotyrosine binding sites are essential for RET/PTC1 to induce thyroid tumor development.     ///    Initial characterization of the thyroid glands of these RET/PTC1 triple-mutant transgenic mice showed no change in follicular morphology or radioiodide-concentrating activity.     ///    "Thyroid tumors in these RET/PTC1 transgenic mice are characterized by a slow growth rate, thyroid-stimulating hormone (TSH)-responsive tumor progression, and loss of radioiodide-concentrating activity despite continued expression of thyroglobulin (Tg). "    ///    Thyroid carcinomas in RET/PTC transgenic mice..     ///    "In high-copy RET/PTC1 transgenic mice, cellular abnormalities, including a slightly increased proliferation rate, aberrant follicle formation, and loss of radioiodide-concentrating activity, can be readily identified at embryological day 18. "    ///    "To identify which signaling pathway or pathways perturbed by RET/PTC1 are essential for RET/PTC1 to induce tumor development, we generated transgenic mice carrying a thyroid-targeted RET/PTC1 triple mutant, which contains tyrosine to phenylalanine mutations at tyrosine residues 294, 404, and 451. "