New form of X-linked dominant hereditary nephritis in dogs

Objective-To determine features of a new form of hereditary nephritis (HN) in dogs. Animals-Parents and 16 first-generation offspring (8 males, 8 females). Procedure-Adolescent dogs that developed renal failure were euthanatized an d necropsied. Unaffected dogs were monitored until they were at least 2 yea rs old. Studies included light and electron microscopy of kidneys obtained from affected and unaffected dogs and immunolabeling for collagen-IV chains in renal and epidermal basement membranes (BM). The nucleotide sequence of a portion of exon 35 of the COL4A5 gene was determined in genomic DNA isol ated from affected and unaffected males. Results-7 of 8 male and 2 of 8 female offspring had proteinuria and juvenil e-onset chronic renal failure, which progressed more rapidly in the males, Labeling for alpha 3-alpha 6(IV) chains was completely absent in renal BM o f affected males and segmentally absent in affected females. Expression of alpha 1-alpha 2(IV) chains in glomerular BM (GBM) of affected dogs was incr eased. Labeling for alpha 5-alpha 6(IV) chains in epidermal BM was absent i n affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GEM of affected dogs. The sequence o f exon 35 of COL4A5 was normal in affected dogs. Conclusions-This renal disease is an example of X-linked dominant HN, with typical abnormalities of GEM ultrastructure and alpha(IV) chain expression. Clinical Relevance and Implications for Human Medicine-Dogs with this natur ally acquired progressive renal disease can be used to investigate the path ogenesis and treatment of similar disorders in human beings and dogs.