Isolation and characterization of a novel gene encoding nuclear protein at a locus (D11S636) tightly linked to multiple endocrine neoplasia type 1 (MEN1)

Abstract

To identify a gene responsible for multiple endocrine neoplasia type 1 (MEN1), we attempted to Isolate potentially transcribable fragments from cosmid clones derived from a region on chromosome 11q13 where genetic linkage studies and analyses of loss of heterozygoslty in MEN 1-associated tumors have localized the MEN1 gene. By an exon-amplification method, we recovered three exon-like sequences from one of these clones, cCI11–367, and using these sequences as probes we were able to Isolate new clones from cerebrum, cerebellum, and fetal-liver cDNA libraries. Sequence analysis of these cDNA clones revealed that the transcribed gene, designated ZFM1, encodes a novel 623-amino-acid protein containing domains with interesting structural properties Including a nuclear transport domain, a metal binding motif, and glutamine- and prollne-rich regions. Analysis by the reverse-transcriptase polymerase chain reaction (RT-PCR) Indicated that this gene is expressed in various tissues including endocrine organs such as thyroid gland, pancreas, adrenal gland, and ovary. These data suggest that ZFM1 might be a candidate for mutations that cause MEN1.