VALIDATION OF A PUTATIVE NEW MODY GENE: TRANSGLUTAMINASE 2 (TGase 2)

The Maturity-Onset Diabetes of the Young (MODY) is an early-onset (ageat diagnosis 25 years), autosomal dominant (it is detected in eachgeneration of the affected family and a mutation in one of the two copiesof DNA is sufficient to cause the disease) subtype of type 2 diabetes(a disease with increase of the glucose values in the bloodstream that leads to severe long-termcomplications to the eyes, kidneys and the heart). Wehave been studying the Italian collection of patients with MODY (350 familiesas of Jan/04) during the past few years. It is predicted that about 50-80.000individuals have MODY in Italy. We know 6 genes that cause MODY but in about 20-25% of MODY patients the gene is unknown. Our group has identified 3 different mutations in a gene encoding for a protein called TGase 2. TGase 2 has been implicated in several different functions: among them TGase 2 may have a role in insulin secretion. Insulin is produced in the pancreatic beta cell and it is the hormone that regulates the glucose levels in the bloodstream. Aim of this project is to discover the molecular mechanism(s) by which mutations of the TGase 2 can impair insulin secretion. Because one of the biological actions of TGase 2 is “protein assembling”, if we will succeed, the next logical step will be the identification of the target protein of TGase 2 actiuon in the pancreatic beta cell.