Primary structure, gene expression and chromosomal mapping of rodent homologs of the MEN1 tumor suppressor gene

Mutations of the MEN1 tumor suppressor gene cause the multiple endocrine ne oplasia type I (MEN1) syndrome in humans, and they are involved in a variet y of sporadic human endocrine tumors. We here characterize the MEN1 gene ho mologs of the mouse and rat, cDNA was isolated from a mouse phage library, and two alternative MEN1 mRNA transcripts containing variant 5' untranslate d regions were identified by RT-PCR in several mouse and rat tissues. When compared to the human molecule, mouse and rat MEN1 (611 and 610 amino acids , respectively) show an overall identity of 96.5% and 97.0% at the protein level, delimiting four conservational domains (A-D). Mouse and rat MEN1 mRN A, as studied by template-calibrated quantitative RT-PCR, is non-exclusivel y expressed in hematopoietic and endocrine cells, with similar expression p atterns found in fetal and adult tissues. Fluorescent in situ hybridization maps the single murine MEN1 locus to chromosome 19, region B. No MEN1 gene mutations were identified in endocrine islet tumor cell lines RIN 5AH (rat ) and NIT-1 (mouse) as compared to wild type cDNA. Our data define mouse an d rat MEN1 as widely expressed and highly conserved homologs of the human M EN1 tumor suppressor gene whose role in biology and endocrine tumorigenesis is due for experimental study. (C) 1999 Elsevier Science B.V. All rights r eserved.