Characterization of the canine <it>CLCN3 </it>gene and evaluation as candidate for late-onset NCL

• Main Authors: Distl Ottmar, Wohlke Anne, Drogemuller Cord
• Format: Article
• Language: English
• Published: BMC 2006-03-01
• Series: BMC Genetics
• Online Access: http://www.biomedcentral.com/1471-2156/7/13
• ISSN: 1471-2156

<p>Abstract</p> <p>Background</p> <p>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 (<it>Clcn3</it>) encoding an intracellular chloride channel was described to cause a phenotype similar to NCL.</p> <p>Results</p> <p>Two full-length cDNA splice variants of the canine <it>CLCN3 </it>gene are reported. The current canine whole genome sequence assembly was used for gene structure analyses and revealed 13 coding <it>CLCN3 </it>exons in 52 kb of genomic sequence. Sequence analysis of the coding exons and flanking intron regions of <it>CLCN3 </it>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 <it>CLCN3 </it>haplotype was associated with NCL.</p> <p>Conclusion</p> <p>For the examined animals we excluded the complete coding region and adjacent intronic regions of canine <it>CLCN3 </it>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.</p>