Localization of Glutamic Acid Decarboxylase in the Kidneys of Nonobese Diabetic Mice

Antibodies to glutamic acid decarboxylase (GAD), a pancreatic islet beta-cell antigen, are present in > 80% of newly diagnosed insulin-dependent diabetes mellitus (IDDM), and are found in nonobese diabetic (NOD) mice, a murine model of spontaneous IDDM. To determine whether GAD is a target antigen in the kidney damage of NOD mice, we studied GAD mRNAs (GAD65 and GAD67) by RT-PCR in mesangial cells, isolated glomeruli, and kidney cortex and medulla in NOD and SJL/C57BL mice. GAD mRNAs were detected in the cortex of both diabetic and nondiabetic NOD and SJL/C57BL mice and GAD antigen was present in proximal and distal tubules by immunofluorescence microscopy. Neither GAD antigen nor mRNA were present in mesangial cells or glomeruli of diabetic or nondiabetic mice. Thus, the expression of GAD in renal tubules raises the possibility that GAD antigens may play a role in diabetic tubulointerstitial disease, whereas the absence of these antigens in glomeruli suggests that GAD-triggered autoimmunity is not directly involved in the glomerular lesions.