Molecular analysis of spontaneous glomerulosclerosis in os/+ mice,
a model with reduced nephron mass.
He, Cijiang, Rudolfs K. Zalups, David A. Henderson#, Gary E. Striker,
and Liliane J. Striker.
Renal Cell Biology Section, Metabolic Diseases Branch, NIDDK, NIH,
Bethesda, MD; Division of Basic Medical Sciences, Mercer University,
School of Medicine, Macon, GA. #Department of Research, College of
Osteopathic Medicine, Oklahoma State University. Tulsa, OK
APStracts 2:0039F, 1995.
ROP Os/+ mice are a radiation-induced mutant strain with reduced
glomerular number and increased glomerular size. We found that they
develop glomerulosclerosis. At 3 months, ROP Os /+ mice had diffuse
mesangial expansion by light microscopy, whereas their +/+
littermates did not. Electron microscopic morphometry revealed a 2
fold increase in mesangial areas, but no changes in the thickness of
glomerular basal laminae. Mean glomerular volume was increased 1.8
fold. Cell number and thymidine labelling index were increased 1.3
and 2.4 fold, respectively. The amount of glomerular type IV collagen
and tenascin, but not laminin, was increased by immunofluorescence
microscopy. mRNA levels in microdissected glomeruli were measured by
competitive RT-PCR and corrected for cell number. [alpha]1IV collagen
and tenascin mRNAs were increased 3.2 fold and 1.8 fold, whereas
laminin B1 mRNA levels were not. The levels of 72 kDa collagenase
mRNA were increased 1.6 fold. TGF-[beta]1 mRNA levels were elevated
1.8 fold, but PDGF-B mRNA levels remained normal. This is the first
analysis of glomerular molecular and cellular changes in a model of
congenital nephron reduction.
Received 8 December 1994; accepted in final form 8 March 1995.
APS Manuscript Number F437-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 March 1995.