Advances in Murine Models of Diabetic Nephropathy

Table 2

Genetically engineered murine models of DN.

Models (Ref)	Strains	Molecular background	Phenotypic alterations	Kidney pathology
OVE26 mice [63–65]	FVB	β-cell-specific damage due to overexpression of calmodulin transgene regulated by the insulin promoter	T1DM, hyperglycemia, hypertension, albuminuria, hypoalbuminemia, and GFR increased first and then decreased	Enlarged glomeruli, enlarging mesangium with diffuse and nodular expansion of mesangial matrix, GBM thickening, diffuse and nodular glomerulosclerosis, nodules similar to typical K-W nodules, expansion of the tubules, atrophy of tubular cells, interstitial infiltration of mononuclear cells, tubulointerstitial fibrosis
eNOS^−/−/db/db mice [66–68]	C57/B6  ×; C57BLKS/J (BKS)	BKS-db/db mice cross with eNOS^−/− mice	T2DM, obesity, hyperglycemia, hypertension, albuminuria, and decreased GFR	Mesangial expansion, GBM thickening, arteriolar hyalinosis, mesangiolysis, microaneurysms, focal segmental and nodular glomerulosclerosis, nodules that resemble K-W nodules, striking fibronectin accumulation in glomeruli, minimal tubulointerstitial fibrosis
RAGE/iNOS mice [45]	CD-1	Transgenic mice that overexpress human RAGE in vascular cells crossbreed with another transgenic line carrying human cDNA for iNOS under the control of the insulin promoter	T1DM,; hyperglycemia,; albuminuria, and increased serum creatinine	Mesangial expansion,; diffuse glomerulosclerosis
Megsin/RAGE/iNOS mice [69]	C57BL/6N ×; CD1	Triple transgenic mice overexpressing megsin, RAGE, and iNOS (megsin transgenic mice crossbreed with RAGE/iNOS transgenic mice)	T1DM,; hyperglycemia,; albuminuria, increased serum creatinine, and urea nitrogen	Glomerular hypertrophy, diffuse mesangial expansion, GBM thickening, global mesangial sclerosis, some segmental sclerotic lesions that resemble K-W nodules, inflammatory cell infiltration, interstitial fibrosis, and immune complexes depositions

eNOS: endothelial nitric oxide synthase; GBM: glomerular basement membrane; GFR: glomerular filtration rate; iNOS: inducible nitric oxide synthase; K-W nodules: Kimmelstiel-Wilson nodules; RAGE: the receptor for advanced glycation endproducts.