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Publication : MafA and MafB regulate genes critical to beta-cells in a unique temporal manner.

First Author  Artner I Year  2010
Journal  Diabetes Volume  59
Issue  10 Pages  2530-9
PubMed ID  20627934 Mgi Jnum  J:169626
Mgi Id  MGI:4941423 Doi  10.2337/db10-0190
Citation  Artner I, et al. (2010) MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes 59(10):2530-9
abstractText  OBJECTIVE: Several transcription factors are essential to pancreatic islet beta-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with beta-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the beta-cell. RESEARCH DESIGN AND METHODS: The distribution of MafA and MafB in the beta-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(-/-) pancreata at embryonic day 18.5, with candidates evaluated by quantitative RT-PCR and in situ hybridization. The potential role of MafA in the expression of verified targets was next analyzed in adult islets of a pancreas-wide MafA mutant (termed MafA(DeltaPanc)). RESULTS: MafB was produced in a larger fraction of beta-cells than MafA during development and found to regulate potential effectors of glucose sensing, hormone processing, vesicle formation, and insulin secretion. Notably, expression from many of these genes was compromised in MafA(DeltaPanc) islets, suggesting that MafA is required to sustain expression in adults. CONCLUSIONS: Our results provide insight into the sequential manner by which MafA and MafB regulate islet beta-cell formation and maturation.
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