Lees G E, Helman R G, Kashtan C E, Michael A F, Homco L D, Millichamp N J, Ninomiya Y, Sado Y, Naito I, Kim Y
Texas Veterinary Medical Center, Texas A&M University, College Station 77843-4474, USA.
Kidney Int. 1998 Sep;54(3):706-19. doi: 10.1046/j.1523-1755.1998.00062.x.
Dogs with naturally occurring genetic disorders of basement membrane (type IV) collagen may serve as animal models of Alport syndrome.
An autosomal recessive form of progressive hereditary nephritis (HN) was studied in 10 affected, 3 obligate carrier, and 4 unaffected English cocker spaniel (ECS) dogs. Clinical, pathological, and ultrastructural features of the disease were characterized. Expression of basement membrane (BM) proteins was examined with an immunohistochemical technique using monospecific antibodies.
Affected dogs had proteinuria and juvenile-onset chronic renal failure. Glomerular basement membrane (GBM) thickening and multilamellation typical of HN were observed in all renal specimens obtained from proteinuric dogs, and severity of GBM ultrastructural abnormalities varied with the clinical stage of disease. Expression of alpha3(IV) and alpha4(IV) chains was totally absent in the kidney of affected dogs. Expression of alpha5(IV) and a6(IV) chains was normal in Bowman's capsule, collecting tubular BM and epidermal BM of affected dogs. The alpha5(IV) chain was not expressed in distal tubular BM of affected dogs. Expression of alpha5(IV) chains was markedly reduced but not absent, and expression of alpha6(IV) chains was present in GBM of affected dogs. Expression of alpha1-alpha2(IV) chains in GBM of affected dogs was increased. Features of obligate carriers were similar to those of unaffected dogs.
We conclude that HN in ECS dogs is a naturally occurring animal model of autosomal recessive Alport syndrome. However, it differs from human disease in the persistence of alpha5(IV) chains in GBM and in the appearance of a6(IV) chains in GBM.
患有天然存在的基底膜（IV型）胶原蛋白遗传疾病的犬类可作为奥尔波特综合征的动物模型。
对10只患病、3只必然携带者和4只未患病的英国可卡犬（ECS）进行了常染色体隐性进行性遗传性肾炎（HN）的研究。对该疾病的临床、病理和超微结构特征进行了表征。使用单特异性抗体的免疫组织化学技术检测基底膜（BM）蛋白的表达。
患病犬出现蛋白尿和幼年起病的慢性肾衰竭。在所有从蛋白尿犬获取的肾脏标本中均观察到HN典型的肾小球基底膜（GBM）增厚和多层化，GBM超微结构异常的严重程度随疾病临床阶段而变化。患病犬肾脏中完全不存在α3（IV）和α4（IV）链的表达。患病犬的鲍曼囊、集合管基底膜和表皮基底膜中α5（IV）和α6（IV）链的表达正常。α5（IV）链在患病犬的远端肾小管基底膜中未表达。α5（IV）链的表达明显减少但未缺失，α6（IV）链在患病犬的GBM中存在表达。患病犬GBM中α1-α2（IV）链的表达增加。必然携带者的特征与未患病犬相似。
我们得出结论，ECS犬的HN是常染色体隐性奥尔波特综合征的天然动物模型。然而，它在GBM中α5（IV）链的持续存在以及GBM中α6（IV）链的出现方面与人类疾病不同。
