Samoyed hereditary glomerulopathy. Immunohistochemical staining of basement membranes of kidney for laminin, collagen type IV, fibronectin, and Goodpasture antigen, and correlation with electron microscopy of glomerular capillary basement membranes.

Recent immunofluorescence studies on the kidneys of most males with hereditary nephritis have demonstrated an absence of Goodpasture antigen (GPA) from glomerular capillary basement membranes (GCBM). In the present study, we used immunofluorescence to determine whether laminin, collagen type IV, fibronectin, and GPA could be detected in basement membranes of the kidneys of dogs with Samoyed hereditary glomerulopathy, which was previously shown to be a model for human hereditary nephritis. The results obtained were correlated with the appearance of GCBM by electron microscopy (EM). The rabbit polyclonal antibodies used (antilaminin, anti-collagen type IV, and antifibronectin) showed specificity for the appropriate antigens in a plate-binding radioimmunoassay. Serum from a patient with Goodpasture syndrome was used to detect the GPA component of dog GCBM. Laminin and collagen type IV were present in GCBM, mesangium, tubular basement membrane, vascular basement membrane, and Bowman's capsule of neonatal, unaffected, and affected male and carrier female dogs. Fibronectin was present in mesangial, perivascular, and interstitial regions of the kidneys of all dogs and, in addition, in GCBM of neonatal, affected male, and carrier female dogs. GPA was not detected in the kidneys of neonatal dogs and its absence from GCBM correlated with their immature appearance by EM. However, a fully formed, trilaminar GCBM was observed by 3 weeks of age in unaffected, affected male, and carrier female dogs, before the detection of GPA in GCBM, which occurred at 4 weeks in unaffected and carrier female dogs, but still not in affected males. In the unaffected dogs, the presence of GPA correlated with the persistence of a fully formed trilaminar GCBM, which lasted throughout life, while in the carrier females, the presence of GPA correlated with focal areas of multilaminar splitting of GCBM by EM. In the affected male dogs, although a trilaminer GCBM was seen by 3 weeks of age, the persistent absence of GPA correlated with the eventual onset of multilaminar splitting of GCBM. These immunofluorescence and EM results suggest that GPA is not required to form a trilaminar GCBM initially but is necessary subsequently to maintain its integrity. GPA is normally present in the C terminal (NC1) domain of the collagen type IV molecule. It is hypothesized that Samoyed hereditary glomerulopathy in dogs and human hereditary nephritis result from a defect in the NC1 domain.