Beta cell-specific expression of retroviral mRNAs and group-specific antigen and the development of beta cell-specific autoimmunity in non-obese diabetic mice.

Abstract

Non-obese diabetic (NOD) mice spontaneously develop autoimmune type 1 diabetes. Earlier studies have shown that retroviruses appear to be associated with the development of the disease in these animals. This investigation was initiated to determine whether any retroviral genes are specifically expressed in pancreatic beta cells from NOD mice, in contrast to their non-diabetic, parental strain, ICR mice. Host chromosomal DNAs from pancreatic islets, kidneys, hearts, and stomachs of NOD and ICR mice contained an equal amount of A-type retroviral genome (DNA); however, A-type retroviral gag, pol, and env mRNAs were detected in only the pancreatic islets from NOD mice. Furthermore, group-specific retroviral antigen (p73 of A-type--gag gene product) was found by immunofluorescent staining using anti-p73 antibody in only pancreatic beta cells from NOD mice. On the basis of these observations, we suggest that tissue and strain differences in transcription of the retroviral genome and beta cell-specific expression of A-type retroviral group-specific antigen p73 in NOD mice may be involved in the initiation of beta cell-specific autoimmunity leading to type 1 diabetes in these animals.