Role of the transcription factor, ARX, on the pancreatic islets and intesitnal endocrine cells

已知转录因子aristaless-related homeobox（ARX）在胰岛细胞的发育中起关键作用。然而，其确切的机制仍有待澄清。我们最近发现，在胰高血糖素基因衍生肽缺乏的小鼠中，显著的增生与胰岛中ARX表达增加相关。在这项研究中，我们试图通过分析两个Arx突变等位基因，有不同程度的功能障碍，以阐明的作用，ARX在α细胞增生。在这些突变小鼠中，胰岛大小和α样细胞数量的增加减少，表明胰高血糖素基因失活诱导的α细胞增生通过引入Arx突变而减少。此外，这种降低与ARX功能受损的严重程度相关，表明ARX的功能是胰腺α细胞增殖的关键调节剂之一。

A transcription factor, aristaless-related homeobox (ARX), is known to play a pivotal role in the development of pancreatic islet cells. However, its precise mechanism remains to be clarified. We recently found that a marked hyperplasia was associated with increased expression of ARX in the pancreatic islet in mice deficient in glucagon gene-derived peptides. In this study, we sought to elucidate the role of ARX in the hyperplasia of alpha cells through analyses of two Arx mutant alleles that have different levels of impairment of their function. The increase in islet size and number of alpha-like cells were reduced in those mutant mice, indicating that the alpha cell hyperplasia induced by the inactivation of glucagon gene is reduced by introduction of an Arx mutation. In addition, the reduction was correlated with severity of disrupted ARX function, showing that the function of ARX is one of the key modifiers for the proliferation of pancreatic alpha cells.