MUTANTS OF GAD65 AND IAN5 RELATING TO DIABETES

摘要

GAD65 mutants which lack a C-terminal conformational epitope are disclosed. The GAD65 mutants can be used in diagnostic methods for detecting the presence of or risk of developing type 1 diabetes. Also disclosed are compositions relating to the Ian5 gene, including Ian5 polynucleotides, Ian5 polypeptides and antibodies thereto, and expression vectors, recombinant cells comprising the Ian5 polynucleotides, and genetically modified animal models. In particular, the compositions include those relating to truncated mutant Ian5 polypeptides lacking a significant portion of the C-terminus. Mutations in the Ian5 gene locus that result in a truncated Ian5 protein are associated with lymphopenia and type 1 diabetes in mammals. The compositions are useful, for example, in methods of screening for agonists or antagonists of Ian5 pathways, such as to identify candidate agents for diabetes drug development, or for developing gene therapy for type 1 diabetes or a related disorder. Also disclosed are diagnostic methods relating to Ian5 gene mutations.