The NC1 domain of collagen type IV in neonatal dog glomerular basement membranes. Significance in Samoyed hereditary glomerulopathy.

摘要

Patients with hereditary nephritis (HN) present with renal disease after infancy, suggesting that the lesion of glomerular basement membranes (GBM) may not be congenital. Therefore, the NC1 domain of collagen type IV in normal neonatal dog GBM was compared with NC1 in normal adult GBM by SDS-PAGE and Western blotting, using two anti-NC1 antibodies. Similar results were obtained, indicating that the NC1 domain is present and immunoreactive in the neonatal period. Next, serial renal biopsies were performed on a family of Samoyed dogs with hereditary glomerulopathy (SHG), an animal model of HN, and assessed by immunofluorescence. One of the anti-NC1 antibodies produced global staining of GBM in unaffected dogs, and global/segmental staining in carrier females; however, no staining was seen in affected males as early as the neonatal period. Electron microscopy (EM) failed to demonstrate any lesion of GBM in neonatal dogs. Thus, in SHG, and presumably in human HN, the abnormality in the NC1 domain is congenital, and precedes the changes seen by EM in GBM.