Localization of extracellular matrix receptors in ICGN mice, a strain of mice with hereditary nephrotic syndrome

Fibrotic degeneration was examined in the kidneys of ICR-derived glomerulon ephritis (ICGN) mice, a novel inbred mouse line with a hereditary nephrotic syndrome of unknown etiology considered to be a good model of human idiopa thic nephrotic syndrome. In the present study, we histochemically revealed changes in accumulation of extracellular matrix (ECM) components and in loc alization of integrins, cellular receptors for ECM, in the kidneys Of ICGN mice with the progression of renal failure. Excessive accumulation of basem ent membrane (laminin and collagen IV) and interstitial (type III collagen) ECM components were demonstrated in the glomeruli and tubulointerstitum of ICGN mice. Marked deposition of type I collagen and tenascin was seen only in the glomeruli of ICGN mice but not in those of ICR mice as normal contr ols. Increased expression of integrin alpha1-, alpha2-, alpha5- and beta1-s ubunits in glomeruli with fibrotic degeneration and abnormal distribution o f alpha6-subunit were noted in the kidneys of ICGN mice. Excessive laminin, a ligand of alpha6 beta1-integrin, was demonstrated on the tubular basemen t membrane, but alpha6-subunit diffusely disappeared on the basal side of t he tubular epithelial cells. We presumed that abnormal integrin expression in renal tubules causes epithelial cell detachment, and consequently tubula r nephropathy, and results in disorder of ECM metabolism causing excessive accumulation of ECM components in the kidneys of ICGN mice.