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本文观看结束!!! Thank you! 谢 谢 欣 赏! * * * First I’d like to show you the structure of Human Pax6 Gene and its cDNA. This gene consists of 13 exons. From the N to the C-terminal sequentially, Pax6 has a paired domain, a homeodomain and a trans-activation region (7, 8). The paired domain along with the homeodomain is the structural basis for binding of Pax6 to the target DNA, and the trans-activation region is able to activate the expression of multiple down-stream genes in the cell . * Pax6 is a transcription factor and is essential of the development of the eye and central nervous system . Homozygous Pax6 mutant animals fail to develop the eye and brain, and die shortly after birth, while heterozygous mutations in Pax6 result in small eyes in mice; aniridia and cerebral malformation in humans. Recently, it has been found that Pax6 is important for pancreatic development and involved in the function of the endocrine pancreas . Pax6 knock-out mice lack α cells , In SeyNeu mutant small eye mice, Pax6 is truncated after the homeodomain, the down-stream gene expression decreased. * Pax6 knock-out mice lack glucagon-producing ? cells and show abnormal islet morphology.In SeyNeu mutant small eye mice, Pax6 is truncated after the homeodomain such that it can bind to the target DNA, but losses the most function of activating the down-stream gene expression. From this graphic, we can see that the expression of glucogan, insulin and somatostatin is much lower than the expression in wild type pancreas. These data suggest that, in addition to the regulation of pancreatic development, Pax6 also plays a role in promotion of insulin expression. * All these observations suggest the possibility that Pax6 mutations may cause diabetes in humans. To date, 6 MODY genes have been identified to cause type 2 diabetes such as NeuroD, Pdx1 and so on. In the present study, we will test the hypothesis that whether Pax6 mutation could lead to development of diabetes and whether Pax6 is a
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