PMID- 20886204 OWN - NLM STAT- MEDLINE DCOM- 20110224 LR - 20211020 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 53 IP - 12 DP - 2010 Dec TI - mRNA expression analysis of cell cycle genes in islets of pregnant mice. PG - 2579-88 LID - 10.1007/s00125-010-1912-8 [doi] AB - AIMS/HYPOTHESIS: Pregnancy requires an increase in the functional beta cell mass to match metabolic needs for insulin. To understand this adaptation at the molecular level, we undertook a time course analysis of mRNA expression in mice. METHODS: Total RNA extracted from C57Bl6/J mouse islets every 3 days during pregnancy was hybridised on commercially available expression arrays. Gene network analysis was performed and changes in functional clusters over time visualised. The function of putative novel cell cycle genes was assessed via silencing in replicating mouse insulinoma 6 (MIN6) cells. RESULTS: Gene network analysis identified a large gene cluster associated with cell cycle control (67 genes, all upregulated by >/= 1.5-fold, p < 0.001). The number of upregulated cell cycle genes and the mRNA expression levels of individual genes peaked at pregnancy day (P)9.5. Filtering of poorly annotated genes with enhanced expression in islets at P9.5, and in MIN6 cells and thymus resulted in further studies with G7e (also known as D17H6S56E-5) and Fignl1. Gene knock-down experiments in MIN6 cells suggested that these genes are indeed involved in adequate cell cycle accomplishment. CONCLUSIONS/INTERPRETATION: A sharp peak of cell cycle-related mRNA expression in islets occurs around P9.5, after which beta cell replication is increased. As illustrated by the identification of G7e and Fignl1 in islets of pregnant mice, further study of this distinct transcriptional peak should help to unravel the complex process of beta cell replication. FAU - Schraenen, A AU - Schraenen A AD - Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Herestraat 49, mailbox 901, 3000 Leuven, Belgium. FAU - de Faudeur, G AU - de Faudeur G FAU - Thorrez, L AU - Thorrez L FAU - Lemaire, K AU - Lemaire K FAU - Van Wichelen, G AU - Van Wichelen G FAU - Granvik, M AU - Granvik M FAU - Van Lommel, L AU - Van Lommel L FAU - in't Veld, P AU - in't Veld P FAU - Schuit, F AU - Schuit F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101001 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (D17H6S56E-5 protein, mouse) RN - 0 (HLA Antigens) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Cell Proliferation MH - Cells, Cultured MH - Female MH - Gene Expression Profiling MH - Gene Knockdown Techniques MH - *Genes, cdc MH - HLA Antigens/genetics/metabolism MH - Insulin-Secreting Cells/metabolism MH - Islets of Langerhans/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Pregnancy MH - RNA, Messenger/analysis/*genetics/metabolism MH - Time Factors PMC - PMC2974927 EDAT- 2010/10/05 06:00 MHDA- 2011/02/25 06:00 PMCR- 2010/10/01 CRDT- 2010/10/02 06:00 PHST- 2010/05/19 00:00 [received] PHST- 2010/08/17 00:00 [accepted] PHST- 2010/10/02 06:00 [entrez] PHST- 2010/10/05 06:00 [pubmed] PHST- 2011/02/25 06:00 [medline] PHST- 2010/10/01 00:00 [pmc-release] AID - 1912 [pii] AID - 10.1007/s00125-010-1912-8 [doi] PST - ppublish SO - Diabetologia. 2010 Dec;53(12):2579-88. doi: 10.1007/s00125-010-1912-8. Epub 2010 Oct 1.