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

摘要: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome, characterized primarily by multiple tumors in the parathyroid glands, pancreas, and anterior pituitary. Other tumors, including gastrinoma, carcinoid, adrenal cortical angiofibroma, collagenoma, lipoma, also occur some patients. Individuals with MEN1 almost always have loss-of-function mutations gene on chromosome 11, arising these patients usually show somatic loss of remaining wild-type allele. To examine role tumor formation, a mouse model was generated through homologous recombination homolog Men1. Homozygous mice die utero at embryonic days 11.5-12.5, whereas heterozygous develop features remarkably similar to those human disorder. As early as 9 months, pancreatic islets range lesions from hyperplasia insulin-producing islet cell adenomas are frequently observed. Larger, more numerous involving islets, parathyroids, thyroid, cortex, pituitary seen 16 months. All tested date Men1 allele, further supporting its suppressor gene.