| A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy. | |
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MedLine Citation:
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PMID: 20582309 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs. |
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Authors:
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Cord Drögemüller; Doreen Becker; Barbara Kessler; Elisabeth Kemter; Jens Tetens; Konrad Jurina; Karin Hultin Jäderlund; Annette Flagstad; Michele Perloski; Kerstin Lindblad-Toh; Kaspar Matiasek |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-22 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-06-28 Completed Date: 2010-09-01 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e11258 Citation Subset: IM |
Affiliation:
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Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne, Switzerland. Cord.Droegemueller@itz.unibe.ch |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle Proteins / genetics* Dog Diseases / genetics* Dogs Female Gene Deletion* Homozygote Intracellular Signaling Peptides and Proteins / genetics* Male Mutation Pedigree Polyneuropathies / genetics, veterinary* Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/N-myc downstream-regulated gene 1 protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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