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SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system


Brons, Ann-Kathrin. SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system. 2013, University of Zurich, Vetsuisse Faculty.

Abstract

Cystinuria, one of the first recognized inborn errors of metabolism, has been reported in many dog breeds. The objective was to determine urinary cystine concentrations, inheritance and mutations in the SLC3A1 and SLC7A9 genes associated with cystinuria in 3 breeds: Mixed and purebred Labrador Retrievers (n=6), Australian Cattle Dogs (6), Miniature Pinschers (4) and one mixed breed dog with cystine urolithiasis, relatives and control dogs. Urinary cystinuria and aminoaciduria was assessed and exons of the SLC3A1 and SLC7A9 genes were sequenced from gDNA. In each breed male and female dogs, independent of neuter status, were found to form calculi. A frameshift mutation in SLC3A1 resulting in a premature stop codon was identified in autosomal-recessive (AR) cystinuria in Labrador Retrievers and mixed breed dogs. A 6 bp deletion removing 2 threonines in SLC3A1 was found in an autosomal-dominant (AD) cystinuria with a more severe phenotype in homozygous than heterozygous Australian Cattle Dogs. A missense mutation in SLC7A9 was discovered in an AD cystinuria in Miniature Pinschers with only heterozygous affected dogs observed to date. Breed specific DNA tests were developed. These studies describe the first AD inheritance and the first putative SLC7A9 mutation to cause cystinuria in dogs and expand our understanding of this phenotypically and genetically heterogeneous disease, leading to a new classification system for canine cystinuria and better therapeutic management and genetic control in these breeds.

Abstract

Cystinuria, one of the first recognized inborn errors of metabolism, has been reported in many dog breeds. The objective was to determine urinary cystine concentrations, inheritance and mutations in the SLC3A1 and SLC7A9 genes associated with cystinuria in 3 breeds: Mixed and purebred Labrador Retrievers (n=6), Australian Cattle Dogs (6), Miniature Pinschers (4) and one mixed breed dog with cystine urolithiasis, relatives and control dogs. Urinary cystinuria and aminoaciduria was assessed and exons of the SLC3A1 and SLC7A9 genes were sequenced from gDNA. In each breed male and female dogs, independent of neuter status, were found to form calculi. A frameshift mutation in SLC3A1 resulting in a premature stop codon was identified in autosomal-recessive (AR) cystinuria in Labrador Retrievers and mixed breed dogs. A 6 bp deletion removing 2 threonines in SLC3A1 was found in an autosomal-dominant (AD) cystinuria with a more severe phenotype in homozygous than heterozygous Australian Cattle Dogs. A missense mutation in SLC7A9 was discovered in an AD cystinuria in Miniature Pinschers with only heterozygous affected dogs observed to date. Breed specific DNA tests were developed. These studies describe the first AD inheritance and the first putative SLC7A9 mutation to cause cystinuria in dogs and expand our understanding of this phenotypically and genetically heterogeneous disease, leading to a new classification system for canine cystinuria and better therapeutic management and genetic control in these breeds.

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Additional indexing

Item Type:Dissertation (monographical)
Referees:Giger Urs
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Department of Small Animals
UZH Dissertations
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Uncontrolled Keywords:metabolic disease, uroliths, nephropathy, hereditary disease
Language:English
Place of Publication:Zürich
Date:2013
Deposited On:02 May 2019 14:50
Last Modified:07 Apr 2020 07:17
Number of Pages:37
OA Status:Green
Related URLs:https://www.recherche-portal.ch/primo-explore/fulldisplay?docid=ebi01_prod009962774&context=L&vid=ZAD&search_scope=default_scope&tab=default_tab&lang=de_DE (Library Catalogue)

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