Strain differences rather than hyperglycemia determine the severity of glomerulosclerosis in mice.
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.
Zheng
F
F
Renal Cell Biology Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
Striker
G E
GE
Esposito
C
C
Lupia
E
E
Striker
L J
LJ
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
D007797:Laminin; D012333:RNA, Messenger; D019063:Tenascin; D003094:Collagen