Thorner P, Baumal R, Binnington A, Valli V E, Marrano P, Clarke H
Department of Pathology, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Am J Pathol. 1989 May;134(5):1047-54.
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.
遗传性肾炎（HN）患者在婴儿期后出现肾脏疾病，这表明肾小球基底膜（GBM）的病变可能并非先天性的。因此，使用两种抗NC1抗体，通过SDS-PAGE和蛋白质印迹法，将正常新生犬GBM中IV型胶原的NC1结构域与正常成年GBM中的NC1进行了比较。获得了相似的结果，表明NC1结构域在新生儿期就已存在且具有免疫反应性。接下来，对患有遗传性肾小球病（SHG，HN的一种动物模型）的萨摩耶犬家族进行了系列肾活检，并通过免疫荧光进行评估。其中一种抗NC1抗体在未受影响的犬中产生GBM的全层染色，在携带致病基因的雌性犬中产生全层/节段性染色；然而，早在新生儿期，患病雄性犬中就未观察到染色。电子显微镜（EM）未能在新生犬中显示GBM的任何病变。因此，在SHG中，大概在人类HN中，NC1结构域的异常是先天性的，并且先于EM在GBM中所见的变化。
