Diabetic nephropathy (DN) is the single most common cause of
end-stage kidney disease. Therefore, it is imperative that novel
therapies are developed. Progress has been hindered, however, by the lack of robust animal models. In the current review we describe recent advances in the field, including the impact of background strain,
hypertension and transcriptomic profiling. While the C57BL/6J strain is relatively resistant to DN, the FVB strain appears more susceptible and Ove26 and db/db mice on this background may be useful in modelling types 1 and 2 DN, respectively. Black and tan,
brachyury (BTBR) mice deficient for the
leptin receptor (ob/ob) develop many of the pathological features of human DN and, remarkably, treatment with exogenous
leptin ameliorates hyperglycaemia,
albuminuria and glomerulosclerosis.
Hypertension plays a key role in the progression of human DN and exacerbates nephropathy in diabetic rodents.
Endothelial nitric oxide synthase deficiency (eNOS(-/-)) results in moderate
hypertension and the development of
nodular glomerulosclerosis and hyaline
arteriosclerosis in
streptozotocin-induced diabetic C57BL/6J mice. In Cyp1a1mRen2 rats,
renin-dependent
hypertension synergises with
streptozotocin-induced hyperglycaemia to produce a 500-fold increase in
albuminuria, glomerulosclerosis and tubulointerstitial
fibrosis. Renal transcriptional profiling suggests that many of the gene expression changes observed in human DN are replicated in eNOS(-/-) mice and Cyp1a1mRen2 rats. Despite these advances, no model faithfully recapitulates all the features of human DN and further refinements are required. In the interim, it is likely that researchers may use publically available transcriptomic data to select the most appropriate model to study their molecule or pathway of interest.