Isolation, genomic organization, and expression analysis of Men1, the murine homolog of the MEN1 gene

The mouse homolog of the human MEN1 gene, which is defective in a dominant familial cancer syndrome, multiple endocrine neoplasia type 1 (MEN1), has b een identified and characterized. The mouse Men1 transcript contains an ope n reading frame encoding a protein of 611 amino acids which has 97% identit y and 98% similarity to human menin. Sequence of the entire Menl gene (9.3 kb) was assembled, revealing 10 exons, with exon I being non-coding; a poly morphic tetranucleotide repeat was located in the 5'- flanking: region. The exon-intron organization and the size of the coding exons 2-9 were well co nserved between the human and mouse genes. Fluorescence in situ hybridizati on localized the Men1 gene to mouse Chromosome (Chr) 19, a region known to be syntenic to human Chr 11q13, the locus for the MEN1 gene. Northern analy sis indicated two messages-2.7 kb and 3.1 kb-expressed in all stages of the embryo analyzed and in all eight adult tissues tested. The larger transcri pt differs from the smaller by the inclusion of an unspliced intron I. Whol e-mount in situ hybridization of 10.5-day and 11.5-day embryos showed ubiqu itous expression of Men1 RNA. Western analysis with antibodies raised again st a conserved C-terminal peptide identified an approximately 67-kDa protei n in the lysates of adult mouse brain, kidney, liver, pancreas, and spleen tissues, consistent with the size of human menin. The levels of mouse menin do not appear to fluctuate during the cell cycle.