title: Strain differences rather than hyperglycemia determine the severity of glomerulosclerosis in mice.
abstract: 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].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Renal Cell Biology Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: F
authors.initials: F
authors.lastname: Zheng
authors.forename: G E
authors.initials: GE
authors.lastname: Striker
authors.forename: C
authors.initials: C
authors.lastname: Esposito
authors.forename: E
authors.initials: E
authors.lastname: Lupia
authors.forename: L J
authors.initials: LJ
authors.lastname: Striker
mesh_terms: D000818:Animals; D002452:Cell Count; D003094:Collagen / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D006943:Hyperglycemia / Q000150:complications*; D007797:Laminin / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D019063:Tenascin / Q000235:genetics
chemical_list: D007797:Laminin; D012333:RNA, Messenger; D019063:Tenascin; D003094:Collagen