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Autoimmune diseases result from a complex interaction between multiple genes and environmental factors. Attempts to identify the genes involved have been largely unsuccessful because of this complexity. This project has chosen to focus on a particular subset of the genes that cause type 1 (autoimmune) diabetes - the subset that control a small population of regulatory white blood cells, termed NKT cells. The applicants have previously shown that a mouse strain prone to diabetes, the NOD mouse st ....Autoimmune diseases result from a complex interaction between multiple genes and environmental factors. Attempts to identify the genes involved have been largely unsuccessful because of this complexity. This project has chosen to focus on a particular subset of the genes that cause type 1 (autoimmune) diabetes - the subset that control a small population of regulatory white blood cells, termed NKT cells. The applicants have previously shown that a mouse strain prone to diabetes, the NOD mouse strain, is deficient in NKT cells and if they are replaced by transfusion, the mice are protected from disease. In selective breeding experiments, they have been able to show that the deficiency in NKT cell numbers is genetic, and have localised the chromosomal positions of these genes. Furthermore, they have produced specially bred lines of NOD mice that have normal copies of these genes and increased numbers of NKT cells. This project aims to identify the genetic coding sequences responsible for controlling numbers of NKT cells. It will use a combination of genetic mapping, specific breeding, gene analyses and the production of genetically modified organisms. The result of this study will be the identification of at least one of the genes that control NKT cell numbers. These gene(s) will then be studied in patients to determine if it plays a role in human disease.Read moreRead less