Molecular biological study of viruses in type 1 disabetes mellitus

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Type 1(insulin-dependent) diabetes mellitus is thought to develop through the mechanisms involving genetics, autoimmunity and viruses. Following our previous reports on the presence of virus-like particles in the NOD mouse (an animal model for type 1 diabetes mellitus), we intended to clone the virus genome and study its expression. NOD mice of 4,6 and 12 weeks of age were examined. Control mice included NON, ICR and B10.G.D.mice. RT-PCR method was used to clone retrovirus cDNA from RNA of the NOD mouse pancreas. PCR cloning was then performed to obtain the retrovirus genome. As a result, we succeeded in cloning the NOD mouse-specific retrovirus (NODV), the sequence of which has not been reported yet. Detailed analysis of NODV revealed following ; NODV is an intrinsic virus incorporated in the NOD mouse genome, its mRNA is expressed only in the pancreas of the NOD mouse, the highest expression of the mRNA is found at 4 weeks of age, i.e.the time when insulitis starts, and LTR of NODV has transcriptional activity in NIT-1 cells derived from NOD mouse beta cells. These results demonstrated the structure and expression of the virus which is thought to be involved in the development of insulitis and diabetes in the NOD mouse. Further analysis of the function of the NODV would disclose the role of viruses in the pathogenesis of type 1 diabetes mellitus.