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  • Author or Editor: R. Gayman Helman x
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in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate expression of the α6 chain of type IV collagen in the glomerular basement membranes (GBM) of healthy dogs.

Sample Population—Kidney specimens from 12 healthy dogs. For comparison, kidney specimens from 8 human subjects between 25 and 83 years old also were evaluated.

Procedure—Sections were immunolabeled with a monospecific antibody that cross-reacts with human and canine α6(IV) chains and examined by means of fluorescence microscopy.

Results—Immunolabeling of the α6(IV) chain was not observed in GBM of 6 dogs ≤ 30 months old but was observed in GBM of the remaining 6 dogs, all of which were ≥ 45 months old. Expression of the α6(IV) chain was not observed in GBM of the human subjects, regardless of the age of the subject.

Conclusions and Clinical Relevance—Results indicate that the α6(IV) chain is expressed in GBM of healthy dogs, but the expression is age-dependent. Composition and structural organization of type IV collagen in the GBM of healthy adult dogs is different from that described for other species. (Am J Vet Res 2000;61:38–41)

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in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

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 and necropsied. Unaffected dogs were monitored until they were at least 2 years 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 isolated from affected and unaffected males.

Results

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. Labeling for α3-α6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of α1-α2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labeling for α5-α6(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.

Conclusions

This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and α(IV) chain expression.

Clinical Relevance and Implications for Human Medicine

Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in human beings and dogs. (Am J Vet Res 1999;60:373–383)

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in American Journal of Veterinary Research