The objectives of this project is to study the functions of two pancreatic-specific genes (PDX-1 and BETA2) during pancreas development. The pancreas is extremely important from the medical point of view, because of its involvement in the two wide-spread diseases, namely, type 1 Insulin-dependent diabetes and pancreatic cancer. Both PDX-1 (pancreatic and duodenal homeobox gene 1) and BETA2 beta-cell epsilon box trans activator for insulin gene. Neonatal pdx-1 mice are apancreatic while the BETA2 pups developed severe hyperglycemia and ketoacidosis, and died within a few days.
The aim of this project is to define more precisely the roles of PDX-1 and BETA2 in pancreas cells commitment and differentiation in vivo. Transgenic mice carrying BETA2 promoter driven PDX-i expression vector or vice versa will be generated. This study will answer the following questions:(1) Would those otherwise alpha, delta and PP (pdx-1-) cells be converted to beta (pdx-1+) cells by overexpression of PDX-1 in these cell types? (2)Would PDX-i - directed ectopic expression of BETA2 in the exocrine precursor cells turns exocrine (beta2) cells into endocrine (beta2+) cells? A study like this will be of considerable benefit to better understand the developmental biology of the pancreas, therefore, the pathogenesis of type 1 diabetes, and eventually, to the treatment of this disease by gene therapy.
