Abdellatif Ahmed M, Ogata Kiyohito, Kudo Takashi, Xiafukaiti Gulibaikelamu, Chang Yu-Hsin, Katoh Megumi C, El-Morsy Salah E, Oishi Hisashi, Takahashi Satoru
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Exp Anim. 2015;64(3):305-12. doi: 10.1538/expanim.15-0001. Epub 2015 Apr 27.
The members of the MAF family of transcription factors are homologs of v-Maf -the oncogenic component of the avian retrovirus AS42. The MAF family is subdivided into 2 groups, small and large MAFs. To elucidate the role of the large MAF transcription factors in the endocrine pancreas, we analyzed large MAF gene knockout mice. It has been shown that Mafa(-/-) mice develop phenotypes including abnormal islet structure soon after birth. This study revealed that Ins1 and Ins2 transcripts and the protein contents were significantly reduced in Mafa(-/-) mice at embryonic day 18.5. In addition, Mafa(-/-);Mafb(-/-) mice contained less than 10% of the insulin transcript and protein of those of wild-type mice, suggesting that Mafa and Mafb cooperate to maintain insulin levels at the embryonic stage. On the other hand, the number of insulin-positive cells in Mafa(-/-) mice was comparable to that of wild-type mice, and even under a Mafb-deficient background the number of insulin-positive cells was not decreased, suggesting that Mafb plays a dominant role in embryonic β-cell development. We also found that at 20 weeks of age Mafa(-/-);Mafb(+/-) mice showed a higher fasting blood glucose level than single Mafa(-/-) mice. In summary, our results indicate that Mafa is necessary for the maintenance of normal insulin levels even in embryos and that Mafb is important for the maintenance of fasting blood glucose levels in the Mafa-deficient background in adults.
转录因子MAF家族的成员是v-Maf的同源物，v-Maf是禽逆转录病毒AS42的致癌成分。MAF家族分为两组，即小MAF和大MAF。为了阐明大MAF转录因子在内分泌胰腺中的作用，我们分析了大MAF基因敲除小鼠。研究表明，Mafa(-/-)小鼠出生后不久就会出现包括胰岛结构异常在内的表型。本研究发现，在胚胎第18.5天，Mafa(-/-)小鼠的Ins1和Ins2转录本以及蛋白质含量显著降低。此外，Mafa(-/-);Mafb(-/-)小鼠的胰岛素转录本和蛋白质含量不到野生型小鼠的10%，这表明Mafa和Mafb在胚胎期协同维持胰岛素水平。另一方面，Mafa(-/-)小鼠中胰岛素阳性细胞的数量与野生型小鼠相当，即使在Mafb缺乏的背景下，胰岛素阳性细胞的数量也没有减少，这表明Mafb在胚胎β细胞发育中起主导作用。我们还发现，在20周龄时，Mafa(-/-);Mafb(+/-)小鼠的空腹血糖水平高于单基因敲除的Mafa(-/-)小鼠。总之，我们的结果表明，Mafa即使在胚胎中对于维持正常胰岛素水平也是必需的，而Mafb对于在成年期Mafa缺乏背景下维持空腹血糖水平很重要。
