Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development
Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development
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DOI：
10.1101/gad.11.13.1662
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发表时间：
1997-07-01
影响因子：
10.5
通讯作者：
German, MS
中科院分区：
文献类型：
--
作者：
Sander, M;Neubuser, A;German, MS
我们提出的遗传和生化证据表明，PAX6是胰岛激素基因转录的关键调节因子，是正常胰岛发育所必需的。在Pax6基因突变等位基因Small eye （Sey(Neu)）纯合的胚胎中，胰腺中所有四种内分泌细胞的数量均显著减少，胰岛形态异常。在剩余的胰岛细胞中，由于基因转录的减少，激素的产生，特别是胰高血糖素的产生明显减少。这些影响似乎是由于突变胚胎中缺乏PAX6蛋白造成的。生化研究发现野生型PAX6蛋白是结合在胰高血糖素、胰岛素和生长抑素启动子中共同元件的转录因子，并表明PAX6可转激活胰高血糖素和胰岛素启动子。
We present genetic and biochemical evidence that PAX6 is a key regulator of pancreatic islet hormone gene transcription and is required for normal islet development. In embryos homozygous for a mutant allele of the Pax6 gene, Small eye (Sey(Neu)), the numbers of all four types of endocrine cells in the pancreas are decreased significantly, and islet morphology is abnormal. In the remaining islet cells, hormone production, particularly glucagon production, is markedly reduced because of decreased gene transcription. These effects appear to result from a lack of PAX6 protein in the mutant embryos. Biochemical studies identify wild-type PAX6 protein as the transcription factor that binds to a common element in the glucagon, insulin, and somatostatin promoters, and show that PAX6 transactivates the glucagon and insulin promoters.