The disorder EIC in Labrador Retrievers is characterized by episodic limb weakness, ataxia, and collapse induced by intense exercise and excitement in young adult, athletic dogs. Recovery is typically rapid, but severe episodes can result in death. Behavior, physical examination findings, and diagnostic test results are unremarkable between EIC episodes.1,2 Until recently, a diagnosis of EIC in Labrador Retrievers was presumptive and made on the basis of a description of clinical signs consistent with EIC and an absence of signs of other identifiable diseases that cause exercise intolerance.3
In 2008, a mutation in the gene encoding the dynamin 1 protein (ie, DNM1) was identified that has a strong, significant association with EIC in Labrador Retrievers.4 This finding indicated a major molecular basis for EIC. Dynamin 1 belongs to a family of enzymes that catalyze hydrolysis of guanosine triphosphate and subsequently undergo conformational changes to form proteins that perform and affect various cellular processes. Dynamin 1 is expressed at synaptic terminal membranes in the CNS and is required for synaptic vesicle endocytosis and neurotransmission during sustained neuronal stimulation (eg, during strenuous exercise).5 The DNM1 mutation (Arg256Leu) identified in Labrador Retrievers has an autosomal recessive mode of inheritance, resulting in clinical disease only in dogs homozygous for this gene mutation.4 A DNA test for identification of the Arg256Leu DNM1 mutation is commercially available and has been used by veterinarians to diagnose the associated disorder known as d-EIC in Labrador Retrievers.6,a
Although collapse during exercise in Labrador Retrievers is frequently attributable to homozygosity for the Arg256Leu DNM1 mutation (d-EIC), some Labrador Retrievers that collapse during exercise do not have that mutation or are heterozygous for the mutation. As for dogs with d-EIC, dogs with recurrent collapse that are not homozygous for the DNM1 mutation may be behaviorally normal and may have unremarkable results of clinical and gait examinations between episodes. In the study4 in which the DNM1 mutation was identified, 33 of the 211 (15.6%) Labrador Retrievers with a history of EIC did not have or were heterozygous for the mutation. The investigators in that study indicated the dogs with a history of EIC that were not homozygous for the DNM1 mutation had collapse episodes that were not typical of those observed for dogs with d-EIC. Further discussion was not provided because complete descriptions of collapse episodes were not available for analysis. Results of a recent study6 indicate as many as one-third of Labrador Retrievers tested for d-EIC that had at least 1 episode of collapse before they were 4 years old did not have or were heterozygous for the DNM1 mutation. However, as for the other report,4 a description of the collapse characteristics was not provided.
The primary objective of the study reported here was to identify characteristics of EIC in Labrador Retrievers and compare characteristics for dogs that are homozygous for the DNM1 mutation with those for dogs that are not homozygous for the mutation. Our hypothesis was that dogs without or heterozygous for the DNM1 mutation would have different characteristics of collapse versus those of dogs that were homozygous for the mutation (ie, dogs with d-EIC). Another objective of the study was to determine whether dogs with episodes of collapse that were not homozygous for the DNM1 mutation had evidence of a distinct neuropathic or myopathic disease.
DNM1-associated exercise-induced collapse
Dynamin 1 gene
Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minn.
JMP Statistical Discovery Software, version 8, SAS Institute Inc, Cary, NC.
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