THYROID PATHOLOGIES IN TRANSGENIC MICE EXPRESSING A HUMAN ACTIVATED RAS GENE DRIVEN BY A THYROGLOBULIN PROMOTER

Four transgenic mice carrying the human activated c-Ha-Ras gene, the e xpression of which was driven into the thyroid gland by a bovine thyro globulin promoter, have been produced. The M1 and M2 mice developed pa pillary thyroid carcinomas and the M2 mouse also developed a lung carc inoma, however none of them transmitted the transgene. Both the M3 and the M4 mice gave rise to transgenic lines. M3 progeny mice develop a goitre with morphological aspects of hyperplasia as well as a thymus h yperplasia, M4 developed a papillary thyroid carcinoma and a lung carc inoma. Lung tumors but not thyroid tumors were observed in M4 adult tr ansgenic progeny. In this M4 line, thyroid dysgenesis leading to growt h retardation and premature death was observed upon serial backcross t hat enhanced the DBA/2J genetic background. The development of thyroid tumors in M1, M2, M4 transgenic mice demonstrates the oncogenic poten tial of activated Ras gene in the thyroid gland. The M4 line raises in teresting questions relative to the interference between the Ras-media ted signal transduction pathway and thyroid morphogenesis.