NOD mice spontaneously develop insulin-dependent diabetes mellitus (IDDM) secondary to immunologically-mediated beta cell destruction in pancreatic islets. Shortly after the appearance of diabetes, NOD mice developed renal lesions consisting of diffuse mesangial sclerosis, thickening of glomerular basement membranes, and the development of albuminuria. These lesions closely mimic those of IDDM in humans. Morphometric analysis showed that the kidney weight and glomerular size were increased in diabetic mice compared to non-diabetic mice, and further, that the ratio glomerular volume/kidney weight was also elevated in diabetic mice. These findings suggest that this disproportionate increase in glomerular size may play an important role in the development of diabetic nephropathy. Preliminary analyses of mRNA levels of matrix proteins, assessed by the RNase protection assay, reveal relative increases in alpha1 type IV collagen, laminin B1, and heparan sulphate proteoglycan. Finally, since the onset of diabetes is variable in NOD mice, we have begun experiments in which we have synchronized the induction of diabetes by the injection of streptozotocin.
