POSITIONAL CLONING OF MEN1 GENE

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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.