Review Article

Advances in Murine Models of Diabetic Nephropathy

Table 1

Murine models of spontaneous DN.

Models (Ref)StrainsDefectsPhenotypic alterationsKidney pathology

NOD mouse
[10, 2832]
Inbred line
derived from
ICR (outbred
line)
Autoimmune insulitis caused by polygenes including specific MHC class II alleles and many non-MHC loci T1DM, hyperglycemia, albuminuria,
autoimmune insulitis, and other autoimmune manifestations
Related reports are few, enlarged glomeruli, and mesangial sclerosis

Insulin-2 Akita mouse
[10, 18, 33]
C57BL/6, C3HAutosomal dominant
mutation in the Ins-2 gene causes misfolding of insulin protein
T1DM, hyperglycemia, and modest levels of albuminuriaIncreased mesangial matrix, GBM thickening, and no mesangiolysis or widespread marked or nodular mesangial sclerosis

db/db mouse
[10, 20, 3337]
C57BL/6,
C57BLKS,
DBA, FVB,
CBA
G-to-T mutation in the gene coding the leptin receptor (db/db)T2DM, hyperglycemia, obesity,and albuminuriaGlomerular hypertrophy, mesangial matrix expansion, GBM thickening, and no mesangiolysis or nodular mesangial sclerosis

OLETF rat
[3840]
Long-Evans Poor pancreatic proliferation caused by multiple genes including several QTLs and the gene encoding CCKART2DM, mild obesity,
late-onset hyperglycemia, macroalbuminuria, hypertension, and dyslipidemia
Glomerular hypertrophy, GBM thickening, extracellular matrix expansion, nodular lesions, diffuse glomerulosclerosis, and severe tubulointerstitial fibrosis

GK rat
[4145]
Wistar Pancreatic beta-cell deficit caused by polygenesT2DM, hypertension,
moderate hyperglycemia, albuminuria, nonobesity,
nonhyperlipidemia
Glomerular hypertrophy and GBM thickening by 35 weeks; segmental glomerulosclerosis and tubulointerstitial fibrosis at 24 months of age

BTBR ob/ob mouse
[4648]
BTBRob/ob mutation (a recessive mutation in the gene coding leptin) in BTBR strainT2DM, severe hyperglycemia,
pancreatic islet hypertrophy, macroalbuminuria, hypercholesterolemia,
elevated triglycerides, obesity, and decreased GFR
Glomerular hypertrophy, mesangial matrix expansion, GBM thickening, loss of podocytes, diffuse mesangial sclerosis (focally approaching nodular glomerulosclerosis), focal mild interstitial fibrosis, focal arteriolar hyalinosis, and mesangiolysis

NZO mouse
[10, 49]
NZOObesity/diabetes caused by polygenes including QTLs on chromosomes 1, 2, 4, 5, 6, 7, 11, 12, 13, 15, 17, and 18 T2DM, obesity, hyperglycemia,
albuminuria, low-titer IgM antibodies to the insulin receptor, and susceptibility to lupus nephritis
Glomerular proliferation, mesangial deposits, mild GBM thickening, glomerulosclerosis, eosinophilic nodules in some glomeruli, occasional hyalinization of the glomerular arterioles, and healing arteriolar inflammation

KK-Ay mouse
[10, 5053]
KK,
C57BL,
C3H,
FVB
Yellow/obese/diabetic phenotype caused by polygenes including dominant mutation in agouti yellow (Ay) geneT2DM, hyperglycemia, obesity, albuminuria, hypertriglyceridemia, and obstructive uropathyGlomerular hypertrophy, mild and moderated mesangial matrix expansion, and segmental proliferative glomerular nephritis

ZDF rat
[5462]
Zuker Missense mutation in the gene coding the leptin receptor (fa/fa)T2DM, hyperglycemia, obesity, hyperlipidemia, hypertension, and macroalbuminuriamesangial expansion, focal segmental glomerulosclerosis, macrophage infiltration, and interstitial fibrosis

CCKAR: cholecystokinin type A receptor; GFR: glomerular filtration rate; GBM: glomerular basement membrane; MHC: major histocompatibility complex; QTLs: quantitative trait loci.