Translating research into personalized care

Home > Phenotyping and Pathophysiology > Kidney Injury Core > Chronic Injury (diabetic) > Type 2 models > eNOS null db/db mice

eNOS null db/db mice > Background Section

 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
View abstract View in PubMed

Functionally significant polymorphisms in endothelial nitric oxide synthase (eNOS) and reduced vascular eNOS activity have been associated with increased human diabetic nephropathy (DN), but the pathogenic role of eNOS deficiency in the development of DN has not yet been confirmed. This study characterizes the severity of DN in eNOS(-/-) mice that were backcrossed to C57BLKS/J db/db mice. Although the severity of hyperglycemia was similar to C57BLKS/J db/db mice, by 26 wk, eNOS(-/-) C57BLKS/J db/db mice exhibited dramatic albuminuria, arteriolar hyalinosis, increased glomerular basement membrane thickness, mesangial expansion, mesangiolysis, and focal segmental and early nodular glomerulosclerosis. Even more remarkable, eNOS(-/-) C57BLKS db/db exhibited decreases in GFR to levels <50% of that in eNOS(+/+) C57BLKS db/db, as confirmed by increased serum creatinine. In summary, eNOS(-/-) db/db mice provide the most robust model of type II DN that has been described to date and support a role for deficient eNOS-derived NO production in the pathogenesis of DN.

ServiceCost (Vanderbilt)Cost (non-Vanderbilt)

Click on the service name to request the service.

Additional content related to eNOS null db/db mice


Last updated on 2013-11-06 Moderated by Raymond Harris