New form of X-linked dominant hereditary nephritis in dogs
Lees, G.E.; Helman, R.G.; Kashtan, C.E.; Michael, A.F.; Homco, L.D.; Millichamp, N.J.; Camacho, Z.T.; Templeton, J.W.; Ninomiya, Y.; Sado, Y.; Naito, I.; Kim, Y.
American Journal of Veterinary Research 60(3): 373-383
1999
ISSN/ISBN: 0002-9645 PMID: 10188823 Document Number: 508236
A new form of canine hereditary nephritis (HN) was investigated in 16 first-generation offspring (8 males, 8 females) and their parents. Adolescent dogs that developed renal failure were examined PM. Unaffected dogs were monitored until they were at least 2 years old. Kidneys from affected and unaffected dogs were examined by light and electron microscopy and immunolabelling 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 isolated from affected and unaffected males. 7 of 8 male and 2 of 8 female offspring had proteinuria and juvenile-onset chronic renal failure, which progressed more rapidly in the males. Labelling for alpha 3- alpha 6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of alpha 1- alpha 2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labelling for alpha 5- alpha 6(IV) chains in epidermal BM was absent in affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GBM of affected dogs. The sequence of exon 35 of COL4A5 was normal in affected dogs. This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and alpha (IV) chain expression. Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in man and dogs.