Strain differences rather than hyperglycemia determine the severity of glomerulosclerosis in mice

Kidney Int. 1998 Dec;54(6):1999-2007. doi: 10.1046/j.1523-1755.1998.00219.x.


Background: We reported that ROP, but not C57, mice were prone to glomerulosclerosis (GS) after nephron reduction (J Clin Invest 97:1242, 1996).

Methods: In this study, we induced diabetes in ROP and C57 mice to determine if the glomerulosclerotic response was stimulus specific. We used the oligosyndactyly mutation (Os), to produce a congenital 50% reduction in nephron number. Stable hyperglycemia was induced by streptozotocin and mice were maintained for 12 weeks without insulin treatment.

Results: Glomerular hypertrophy occurred in diabetic ROP +/+ and C57 +/+ mice, but glomeruli of diabetic ROP +/+ mice had 1.92-fold higher laminin B1 and 1.5-fold higher tenascin mRNA levels than diabetic C57 +/+ mice. Diabetic ROP Os/+ mice had severe glomerulosclerosis with arteriolar and tubulointerstitial lesions while there was only moderate mesangial sclerosis in diabetic C57 Os/+ mice. Glomerular size was increased in all non-diabetic Os/+ mice. It was further increased in diabetic ROP Os/+ mice, but not in diabetic C57 Os/+ mice. Glomerular mRNA levels were higher in diabetic ROP OS/+ than in diabetic C57 OS/+ mice [alpha 1 (i.v.) collagen 3.2-fold, laminin B1 2.1-fold, and tenascin 1.6-fold].

Conclusion: Overall, our data further support the hypothesis that the susceptibility to glomerulosclerosis is inherited, and suggest that hyperglycemia serves principally as a triggering event in the development of diabetic nephropathy. Since the acceleration of diabetic nephropathy by nephron reduction was also largely strain dependent, it appears that the propensity to glomerulosclerosis is a general renal response and is not stimulus specific.

MeSH terms

  • Animals
  • Cell Count
  • Collagen / genetics
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology*
  • Glomerulosclerosis, Focal Segmental / blood*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Glomerulosclerosis, Focal Segmental / physiopathology*
  • Hyperglycemia / complications*
  • Laminin / genetics
  • Mice
  • Mice, Inbred Strains / physiology*
  • RNA, Messenger / metabolism
  • Tenascin / genetics


  • Laminin
  • RNA, Messenger
  • Tenascin
  • Collagen