Funding outcome

The pancreas has many important functions, including exocrine and endocrine. Exocrine functions include secreting enzymes into the small intestine that are needed for digestion (such as lipases for fat, amylase for starch and proteases for proteins) and endocrine functions include releasing hormones into the bloodstream that control our blood sugar levels (for example, insulin and glucagon). In the mouse and humans, pancreatic endocrine cells are located in special islands in the pancreas called the islets of Langerhans. It is interesting to know that the mouse has two insulin genes whereas humans have only one insulin gene. There are several genes encoding proteins called transcription factors that control the development of the pancreas, including the islets. Transcription factors are 'molecular switches' that turn target genes 'on' or 'off'. In some cases, patients with mutations of these genes have a type of Type 2 diabetes called Maturity Onsent Diabetes of the Young (MODY). The Eisenstat lab in the Department of Medical Genetics is studying the role of the DLX genes during mouse development. DLX genes code for DLX transcription factors. Preliminary data from the lab shows decreased insulin expression in a mouse missing two of the DLX genes (DLXl and DLX2). Using cells from embryonic mouse pancreas, they have also discovered that DLX2 binds to the genes for insulin-1 and insulin-2. Unfortunately, the DLX1/DLX2 double gene knockout mouse dies at birth so we do not yet know if these mice have a tendency to become diabetic. In my project, I will work out how the loss of DLX gene function affects development of the pancreatic islets and I will also study how the DLX2 gene directly regulates both of the mouse insulin genes using special biochemistry and molecular biology approaches in my experiments.