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A novel model of autosomal dominant Alport syndrome in Dalmatian dogs
Journal article   Peer reviewed

A novel model of autosomal dominant Alport syndrome in Dalmatian dogs

J.C. Hood, C. Huxtable, I. Naito, C. Smith, R. Sinclair and J. Savige
Nephrology Dialysis Transplantation, Vol.17(12), pp.2094-2098
2002
DOI: https://doi.org/10.1093/ndt/17.12.2094
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Abstract

Background. Autosomal dominant Alport syndrome is a rare inherited disease characterized clinically by haematuria, renal failure and deafness, and ultrastructurally by a lamellated glomerular basement membrane (GBM). It is usually caused by mutations in the COL4A3 or COL4A4 genes which code for the α3 and α4 chains of type IV collagen. We describe here a novel spontaneous model of autosomal dominant Alport syndrome in Dalmatian dogs. Methods. Affected dogs were identified by a urinary protein creatinine ≥0.3. A total of 10 affected adult Dalmatians and eight unaffected age- and sex-matched dogs from breeds other than Dalmatians were examined. In addition, kidneys from five Dalmatian fetuses from affected mothers were examined histologically and ultrastructurally. Results. All affected dogs were purebred Dalmatians and had a common progenitor. Successive generations were affected, and males and females were affected equally often and equally severely, consistent with autosomal dominant inheritance. The median age at onset of renal failure was 18 months (range 8 months to 7 years). Affected dogs were not clinically deaf, and did not have the ocular abnormalities seen in human X-linked or autosomal recessive Alport syndrome. In addition, they did not have the leucocyte inclusions, low platelet counts or large platelets seen in autosomal dominant hereditary nephritis due to MYH9 mutations. The renal histology and ultrastructural appearance of the GBM appeared to be normal in utero. However, affected adult kidneys demonstrated segmental glomerular hyalinosis and sclerosis with tubulo-interstitial inflammation and fibrosis, and on ultrastructural examination the GBM was lamellated with subepithelial frilling, vacuolation and occasional intramembranous deposits. All α1(IV)-α5(IV) type IV collagen chains were present in the affected GBM and Bowman's capsule. Conclusions. Autosomal dominant Alport syndrome in Dalmatians resembles the disease in Bull terriers but has arisen independently. These models will enable us to determine how genetic mutations affect the corresponding proteins and overall membrane structure in autosomal dominant Alport syndrome.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.132 Extracellular Matrix & Cell Differentiation
1.132.1373 Alport Syndrome
Web Of Science research areas
Transplantation
Urology & Nephrology
ESI research areas
Clinical Medicine
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