A MODEL OF AUTOSOMAL RECESSIVE ALPORT-SYNDROME IN ENGLISH COCKER-SPANIEL DOGS

Background. Dogs with naturally occurring genetic disorders of basemen t membrane (type IV) collagen may serve as animal models of Alport syn drome. Methods. An autosomal recessive form of progressive hereditary nephritis (HN) was studied in 10 affected, 3 obligate carrier, anti 4 unaffected English cocker spaniel (ECS) dogs. Clinical, pathological, and ultrastructural features of the disease were characterized. Expres sion of basement membrane (BM) proteins was examined with an immunohis tochemical technique using monospecific antibodies. Results, Affected dogs had proteinuria and juvenile-onset chronic renal failure, Glomeru lar basement membrane (GBM) thickening and multilamellation typical of HN were observed in all renal specimens obtained from proteinuric dog s, and severity of GEM ultrastructural abnormalities varied with the c linical stage of disease. Expression of alpha 3(IV) and alpha 4(IV) ch ains was totally absent in the kidney of affected dogs. Expression of alpha 5(IV) and alpha 6(IV) chains was normal in Bowman's capsule, col lecting tubular BM and epidermal BM of affected dogs, The alpha 5(IV) chain was not expressed in distal tubular BM of affected dogs. Express ion of a alpha(IV) chains was markedly reduced but not absent, and exp ression of alpha 6(IV) chains was present in GBM of affected dogs. Exp ression of alpha 1-alpha 2(IV) chains in GBM of affected dogs was incr eased. Features of obligate carriers were similar to those of unaffect ed dogs.Conclusions. We conclude that HN in ECS dogs is a naturally oc curring animal model of autosomal recessive Alport syndrome. However, it differs from human disease in the persistence of alpha 5(IV) chains in GEM and in the appearance of alpha 6(IV) chains in GBM.