Molecular analysis of spontaneous glomerulosclerosis in Os/+ mice, a model with reduced nephron mass.
Oligosyndactyly mice (ROP Os/+) are a radiation-induced mutant strain with reduced glomerular number and increased glomerular size. We found that they develop glomerulosclerosis. At 3 mo, ROP Os/+ mice had diffuse mesangial expansion by light microscopy, whereas their +/+ littermates did not. Electron microscopic morphometry revealed a twofold 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 labeling 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 competetive reverse transcription-polymerase chain reaction and corrected for cell number. alpha 1-Chain type IV 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. Transforming growth factor-beta 1 mRNA levels were elevated 1.8-fold, but platelet-derived growth factor-B mRNA levels remained normal. This is the first analysis of glomerular molecular and cellular changes in a model of congenital nephron reduction.
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Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1268, USA.
Zalups
R K
RK
Henderson
D A
DA
Striker
G E
GE
Striker
L J
LJ
D000199:Actins / Q000235:genetics; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D003094:Collagen / Q000235:genetics; D017364:Collagenases / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology*; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D009399:Nephrons / Q000473:pathology*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D019063:Tenascin
D000199:Actins; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D019063:Tenascin; D003094:Collagen; D017364:Collagenases