PMID- 9824159 OWN - NLM STAT- MEDLINE DCOM- 19981210 LR - 20061115 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 17 IP - 19 DP - 1998 Nov 12 TI - Characterization of the mouse Men1 gene and its expression during development. PG - 2485-93 AB - The gene responsible for multiple endocrine neoplasia type 1 (MEN1), a heritable predisposition to endocrine tumours in man, has recently been identified. Here we have characterized the murine homologue with regard to cDNA sequence, genomic structure, expression pattern and chromosomal localisation. The murine Men1 gene spans approximately 6.7 kb of genomic DNA and is comprised of 10 exons with similar genomic structure to the human locus. It was mapped to the pericentromeric region of mouse chromosome 19, which is conserved with the human 11q13 band where MEN1 is located. The predicted protein is 611 amino acids in length and overall is 97% homologous to the human orthologue. The 45 reported MEN1 mutations which alter or delete a single amino acid in human all occur at conserved residues, thereby supporting their functional significance. Two transcripts of approximately 3.2 and 2.8 kb were detected in both embryonal and adult murine tissues, resulting from alternative splicing of intron 1. By RNA in situ hybridization and Northern analysis the spatiotemporal expression pattern of Men1 was determined during mouse development. Men1 gene activity was detected already at gestational day 7. At embryonic day 14 expression was generally high throughout the embryo, while at day 17 the thymus, skeletal muscle, and CNS showed the strongest signal. In selected tissues from postnatal mouse Men1 was detected in all tissues analysed and was expressed at high levels in cerebral cortex, hippocampus, testis, and thymus. In brain the menin protein was detected mainly in nerve cell nuclei, whereas in testis it appeared perinuclear in spermatogonia. These results show that Men1 expression is not confined to organs affected in MEN1, suggesting that Men1 has a significant function in many different cell types including the CNS and testis. FAU - Stewart, C AU - Stewart C AD - Queensland Cancer Fund Research Laboratories, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston, Australia. FAU - Parente, F AU - Parente F FAU - Piehl, F AU - Piehl F FAU - Farnebo, F AU - Farnebo F FAU - Quincey, D AU - Quincey D FAU - Silins, G AU - Silins G FAU - Bergman, L AU - Bergman L FAU - Carle, G F AU - Carle GF FAU - Lemmens, I AU - Lemmens I FAU - Grimmond, S AU - Grimmond S FAU - Xian, C Z AU - Xian CZ FAU - Khodei, S AU - Khodei S FAU - Teh, B T AU - Teh BT FAU - Lagercrantz, J AU - Lagercrantz J FAU - Siggers, P AU - Siggers P FAU - Calender, A AU - Calender A FAU - Van de Vem, V AU - Van de Vem V FAU - Kas, K AU - Kas K FAU - Weber, G AU - Weber G FAU - Hayward, N AU - Hayward N FAU - Gaudray, P AU - Gaudray P FAU - Larsson, C AU - Larsson C LA - eng SI - GENBANK/AF016398 SI - GENBANK/AF024513 PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (DNA, Complementary) RN - 0 (MEN1 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Amino Acid Sequence MH - Animals MH - Brain/embryology/metabolism MH - Chromosome Mapping MH - DNA, Complementary/genetics MH - Female MH - *Gene Expression Regulation, Developmental MH - Gene Library MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Mice/embryology/*genetics/growth & development MH - Molecular Sequence Data MH - Neoplasm Proteins/*biosynthesis MH - Nerve Tissue Proteins/biosynthesis/genetics MH - Organ Specificity MH - *Proto-Oncogene Proteins MH - *Proto-Oncogenes MH - RNA Splicing MH - RNA, Messenger/biosynthesis MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Species Specificity MH - Testis/embryology/metabolism EDAT- 1998/11/21 00:00 MHDA- 1998/11/21 00:01 CRDT- 1998/11/21 00:00 PHST- 1998/11/21 00:00 [pubmed] PHST- 1998/11/21 00:01 [medline] PHST- 1998/11/21 00:00 [entrez] AID - 10.1038/sj.onc.1202164 [doi] PST - ppublish SO - Oncogene. 1998 Nov 12;17(19):2485-93. doi: 10.1038/sj.onc.1202164.