POSITIONAL CLONING OF MEN1 GENE

MEN1 基因的定位克隆

• 批准号: 6108959
• 负责人: settara chandrasekharappa
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6108959
• 关键词: artificial chromosomes; autosomal dominant trait; fluorescent in situ hybridization; gene expression; gene mutation; genetic library; genetic mapping; genetic markers; human genetic material tag; linkage disequilibriums; loss of heterozygosity; molecular cloning; multiple endocrine neoplasia; neoplasm /cancer genetics; nucleic acid probes; nucleic acid sequence; sequence tagged sites

We have shown that inherited mutations in the MEN1 gene predispose individuals to develop multiple endocrine neoplasia type 1 (MEN1), characterized by multiple tumors of the parathyroid, gastrointestinal (GI) endocrine, and anterior pituitary tissues. The amino acid sequence of the MEN1 encoded protein (menin) does not provide clues as to its function. We have shown that menin is located primarily in the nucleus, and two functionally independent nuclear localization signals (NLS), located in the C-terminal quarter of the protein, have been identified. In order to understand the functional role of menin, a mouse knock-out model is being generated by homologous recombination. Also the zebrafish homolog of the menin gene has been isolated and its role in zebrafish embryonic development is being studied. In addition, potential interactions of menin with other cellular proteins are being investigated by yeast two- hybrid system, immunoprecipitation and GST­menin pull-down assays. Characterization of the interacting proteins is in progress.

我们已经证明了遗传突变