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.