title: Characterization of the canine CLCN3 gene and evaluation as candidate for late-onset NCL.
abstract: BACKGROUND
  The neuronal ceroid lipofuscinoses (NCL) are a heterogenous group of inherited progressive neurodegenerative diseases in different mammalian species. Tibetan Terrier and Polish Owczarek Nizinny (PON) dogs show rare late-onset NCL variants with autosomal recessive inheritance, which can not be explained by mutations of known human NCL genes. These dog breeds represent animal models for human late-onset NCL. In mice the chloride channel 3 gene (Clcn3) encoding an intracellular chloride channel was described to cause a phenotype similar to NCL.
  
  
  RESULTS
  Two full-length cDNA splice variants of the canine CLCN3 gene are reported. The current canine whole genome sequence assembly was used for gene structure analyses and revealed 13 coding CLCN3 exons in 52 kb of genomic sequence. Sequence analysis of the coding exons and flanking intron regions of CLCN3 using six NCL-affected Tibetan terrier dogs and an NCL-affected Polish Owczarek Nizinny (PON) dog, as well as eight healthy Tibetan terrier dogs revealed 13 SNPs. No consistent CLCN3 haplotype was associated with NCL.
  
  
  CONCLUSIONS
  For the examined animals we excluded the complete coding region and adjacent intronic regions of canine CLCN3 to harbor disease-causing mutations. Therefore it seems to be unlikely that a mutation in this gene is responsible for the late-onset NCL phenotype in these two dog breeds.
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Bünteweg 17p, 30559 Hannover, Germany. anne.woehlke@tiho-hannover.de
authors.forename: Anne
authors.initials: A
authors.lastname: Wohlke
authors.forename: Ottmar
authors.initials: O
authors.lastname: Distl
authors.forename: Cord
authors.initials: C
authors.lastname: Drogemuller
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004285:Dogs; D005091:Exons; D020022:Genetic Predisposition to Disease; D007438:Introns; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D018118:Chloride Channels