| Abstract: | The members of the MAF family of transcription factors are homologs of v-Maf –theoncogenic component of the avian retrovirus AS42. The MAF family is subdivided into 2groups, small and large MAFs. To elucidate the role of the large MAF transcription factorsin the endocrine pancreas, we analyzed large MAF gene knockout mice. It has been shownthat Mafa−/− mice develop phenotypes including abnormal isletstructure soon after birth. This study revealed that Ins1 andIns2 transcripts and the protein contents were significantly reduced inMafa−/− mice at embryonic day 18.5. In addition,Mafa−/−;Mafb−/− mice containedless than 10% of the insulin transcript and protein of those of wild-type mice, suggestingthat Mafa and Mafb cooperate to maintain insulin levelsat the embryonic stage. On the other hand, the number of insulin-positive cells inMafa−/− mice was comparable to that of wild-type mice, andeven under a Mafb-deficient background the number of insulin-positivecells was not decreased, suggesting that Mafb plays a dominant role inembryonic β-cell development. We also found that at 20 weeks of ageMafa−/−;Mafb+/− mice showed ahigher fasting blood glucose level than single Mafa−/− mice.In summary, our results indicate that Mafa is necessary for themaintenance of normal insulin levels even in embryos and that Mafb isimportant for the maintenance of fasting blood glucose levels in theMafa-deficient background in adults. |
