Foxa2 is required for the differentiation of pancreatic α-cells
Foxa2 is required for the differentiation of pancreatic α-cells
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DOI：
10.1016/j.ydbio.2004.10.012
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发表时间：
2005-02-15
影响因子：
2.7
通讯作者：
Kaestner, KH
中科院分区：
文献类型：
--
作者：
Lee, CS;Sund, NJ;Kaestner, KH
产生胰岛素的β细胞的分化已被详细研究；然而，对于第二丰富的内分泌谱系，即产生胰高血糖素的α细胞，所知甚少。在这里，我们利用一种新的基于yac的Foxa3Cre转基因来删除妊娠中期胰腺原基中的带翼螺旋转录因子Foxa2（以前称为HNF-3beta）。得到Foxa2(loxP/loxP)；Foxa3Cre小鼠严重低血糖，在出生后一周内死亡。突变小鼠低胰高血糖素血症继发于胰高血糖素表达减少90%。虽然成熟胰高血糖素阳性α细胞的数量显著减少，但α细胞祖细胞的特异性不受Foxa2缺乏的影响。通过标记基因分析，我们发现u细胞转录因子Arx、Pax6和Brn4的表达在控制α细胞分化的转录层次中不需要Foxa2。(C) 2004爱思唯尔公司版权所有。
The differentiation of insulin-producing beta-cells has been investigated in great detail; however, little is known about the factors that delineate the second-most abundant endocrine lineage, the glucagon-producing alpha-cell. Here we utilize a novel YAC-based Foxa3Cre transgene to delete the winged helix transcription factor Foxa2 (formerly HNF-3beta) in the pancreatic primordium during midgestation. The resulting Foxa2(loxP/loxP); Foxa3Cre mice are severely hypoglycemic and die within the first week of life. Mutant mice are hypoglucagonemic secondary to a 90% reduction of glucagon expression. While the number of mature glucagon-positive alpha-cells is dramatically reduced, specification of alpha-cell progenitors is not affected by Foxa2 deficiency. By marker gene analysis, we show that the expression of the U-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation. (C) 2004 Elsevier Inc. All rights reserved.