eNOS db/db

 Functionally significant polymorphisms in endothelial nitric oxide synthase (eNOS) and reduced vascular endothelial nitric oxide synthase (eNOS) activity have been associated with increased incidence and progression of human diabetic nephropathy. In a recently published study, we have determined that in a model of type II diabetes, deletion of the eNOS gene led to significant decreases in GFR and increases in albuminuria, arteriolar hyalinosis, increased GBM thickness, mesangial expansion, mesangiolysis and focal segmental and early nodular glomerulosclerosis (1).  To generate these mice, eNOS+/- mice were backcrossed for 10 generations to the C57BLKS background and then crossed with db heterozygous mice on the same background.  eNOS db/db mice have progressive functional and structural  renal abnormalities over the next 16 weeks. By 26 weeks, there is significant renal histologic damage (see Figure 1) Therefore this model of type II diabetes offers the advantage that significant pathologic abnormalities can be detected within a relatively short time period compared to previous mouse or rat models of diabetes. Testing a potential therapeutic intervention can therefore be assessed with 8-16 weeks of treatment.

Publications for eNOS null db/db mice (1)

Zhao HJ, Wang S, Cheng H, Zhang MZ, Takahashi T, Fogo AB, Breyer MD, Harris RC. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice. J Am Soc Nephrol (2006) 17:2664-9
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Background
Literature