We have previously reported that mice transgenic for growth hormone develop a rapidly progressive glomerulosclerosis. In contrast, mice transgenic for a mutated growth hormone (G 119K) have a dwarf phenotype and have normal glomeruli. We postulated that growth hormone was required for the appearance of glomerulosclerosis and that the dwarf mice would be protected from diabetic renal lesions. We made normal non- transgenic mice diabetic by using repeated streptozotocin injections. The mice were kept alive 3 months without insulin treatment. The glomeruli showed marked hypertrophy and diffuse mesangial lesions with appearance of nodules characteristic of diabetic nephropathy. The dwarf transgenic mice were also made diabetic but failed to develop glomerular hypertrophy and glomerular lesions. These data show that the GH antagonist which is expressed at high levels in the transgenic mice completely prevents the development of diabetic glomerulosclerosis. Furthermore, immunofluorescence microscopy showed accumulation of type IV collagen and laminin in the control, but not in the transgenic mice. Competitive PCR of microdissected glomeruli was performed in order to examine genes coding for laminin B1, alpha1 Type IV collagen and showed that they were elevated in the control but not in transgenic mice.
