Characterization of the MEN1 ortholog in zebrafish

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrom e predisposing to multiple tumors. The responsible gene, MEN1, has been ide ntified and inactivating mutations reported. It encodes a protein named men in, which lacks homology to any known proteins. Comparative genomics is use d to ascertain important functional domains via the identification of evolu tionary conserved regions. Here we report the sequencing and characterizati on of the MEN1 gene in zebrafish (Danio rerio) at the cDNA level. Zebrafish menin is a 617 amino acid protein and, when compared with human and rodent proteins, shows 75% and 76% similarity, respectively. The most conserved r egion is amino acid residues 41-322 which shows a human/zebrafish similarit y of 83%. Amino acids affected by inactivating missense mutations in MEN1 p atients in this region are completely conserved between human and zebrafish . Such high correlation between conservation throughout evolution and mutat ion position strongly emphasizes the importance of this region. (C) 1999 Ac ademic Press.