A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome, characterized primarily by multiple tumors in the parathyroid gla nds, endocrine pancreas, and anterior pituitary. Other tumors, including ga strinoma, carcinoid, adrenal cortical tumors, angiofibroma, collagenoma, an d lipoma, also occur in some patients. Individuals with MEN1 almost always have loss-of-function mutations in the MEN1? gene on chromosome 11, and end ocrine tumors arising in these patients usually show somatic loss of the re maining wild-type allele. To examine the role of MEN1 in tumor formation, a mouse model was generated th rough homologous recombination of the mouse h omolog Men 1. Homozygous mice die in utero at embryonic days 11.5-12.5, whe reas heterozygous mice develop features remarkably similar to those of the human disorder. As early as 9 months, pancreatic islets show a range of les ions from hyperplasia to insulin-producing islet cell tumors, and parathyro id adenomas are also frequently observed. Larger, more numerous tumors invo lving pancreatic islets, parathyroids, thyroid, adrenal cortex, and pituita ry are seen by 16 months. All of the tumors tested to date show loss of the wild-type Men1 allele, further supporting its role as a tumor suppressor g ene.