Laboratory Investigation

Kidney International (1995) 47, 758–765; doi:10.1038/ki.1995.116

Bull terrier hereditary nephritis: A model for autosomal dominant Alport syndrome

Jennifer C Hood, Judy Savige, Anne Hendtlass, Mary M Kleppel, Clive R Huxtable and Wayne F Robinson

Section of Pathology, School of Veterinary Studies, Murdoch University, Perth, Western Australia, and *University Department of Medicine, Austin Hospital, Melbourne, Victoria, Australia; and Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence: Jennifer Hood BSc, Hon BVMS, Section of Pathology, School of Veterinary Studies, Murdoch University, Murdoch, Western Australia, Australia.

Received 15 July 1994; Revised 15 October 1994; Accepted 31 October 1994.

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Abstract

Bull terrier hereditary nephritis: A model for autosomal dominant Alport syndrome. Bull terrier hereditary nephritis is inherited as an autosomal dominant disease and causes renal failure at variable ages in affected dogs. The aims of this study were to compare the clinical, ultrastructural and immunohistochemical features of bull terrier hereditary nephritis with the characteristics of the human forms of Alport syndrome. Many animals with bull terrier hereditary nephritis have hematuria, and some have anterior lenticonus. However, deafness is not associated with the renal disease, and affected dogs do not have the large platelets that are occasionally seen in patients with autosomal Alport syndrome. The glomerular capillary basement membrane (GCBM) in affected bull terriers has an identical ultrastructural appearance to that seen in X-linked Alport syndrome, with lamellations and intramembranous electron-dense deposits. However, both the Goodpasture and the Alport antigens, which represent parts of the alpha 3(IV) and alpha 5 (IV) collagen chains, respectively, are present in the GCBM of affected dogs. Bull terrier hereditary nephritis represents an animal model for autosomal dominant Alport syndrome, and can be used to further examine how genetic mutations affect a basement membrane protein and the corresponding membrane structure.

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