PMID- 11712086 OWN - NLM STAT- MEDLINE DCOM- 20020306 LR - 20071115 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 8 IP - 6 DP - 2001 Dec TI - Differential expression of multiple alternative spliceforms of the Men1 tumor suppressor gene in mouse. PG - 681-9 AB - The multiple endocrine neoplasia type 1 gene (MEN1) is a tumor suppressor gene associated with the development of tumors in the parathyroids, the pituitary, and the pancreas and has also been linked to impaired germ cell production. The murine ortholog, Men1, is highly homologous to the human counterpart both at DNA and protein levels. The present study was undertaken to further approach the function of Men1 and its encoded protein menin. By 5' RACE and RT-PCR four alternative splice variants were identified, indicating a 5' heterogeneity of Men1 similar to the human counterpart. By mRNA in situ hybridization of embryonal and adult mouse tissues, all four splice variants were shown to be expressed, albeit at varying timepoints and levels in the different tissues. However, a putative isoform postulated from the DNA sequence, which would elongate the reading frame by 15 bases at the exon 2/intron 2 junction, was not found to occur in mouse. The strongest expression was detected in testis, both at the mRNA and protein level and was therefore further characterized by protein analysis of cells isolated from different stages of the spermatogenesis. Western blotting revealed a single protein of approximately 70 kDa detected in total testis, isolated pachytene spermatocytes and in haploid spermatids. Notably, no menin expression was detectable in the extracts from epididymis where the maturation of sperms is almost completed, suggesting that menin plays a crucial role during spermatogenesis. FAU - Forsberg, L AU - Forsberg L AD - Department of Molecular Medicine, Endocrine tumor unit, Karolinska Hospital CMM L8:01, SE-171 76 Stockholm, Sweden. lars.forsberg@cmm.ki.se FAU - Zablewska, B AU - Zablewska B FAU - Piehl, F AU - Piehl F FAU - Weber, G AU - Weber G FAU - Lagercrantz, S AU - Lagercrantz S FAU - Gaudray, P AU - Gaudray P FAU - Hoog, C AU - Hoog C FAU - Larsson, C AU - Larsson C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (MEN1 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Protein Isoforms) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) SB - IM MH - *Alternative Splicing MH - Animals MH - Blotting, Northern MH - Blotting, Western MH - Embryo, Mammalian/metabolism MH - Female MH - Gene Expression Regulation MH - Gene Expression Regulation, Developmental MH - Genes, Tumor Suppressor MH - In Situ Hybridization MH - Male MH - Mice MH - Mice, Inbred Strains MH - Neoplasm Proteins/*genetics/metabolism MH - Pregnancy MH - Protein Isoforms/genetics/metabolism MH - *Proto-Oncogene Proteins MH - RNA, Messenger/genetics/metabolism MH - Spermatogenesis/genetics MH - Tissue Distribution EDAT- 2001/11/17 10:00 MHDA- 2002/03/07 10:01 CRDT- 2001/11/17 10:00 PHST- 2001/11/17 10:00 [pubmed] PHST- 2002/03/07 10:01 [medline] PHST- 2001/11/17 10:00 [entrez] PST - ppublish SO - Int J Mol Med. 2001 Dec;8(6):681-9.