00993-A: Dynactin Mutations in Canine Idiopathic Laryngeal Paralysis

Grant Amount: $12,960

David E Holt, BVSc; University of Pennsylvania

July 1, 2007 - June 30, 2008

Sponsor(s):

Breed(s): Leonberger, Labrador Retriever

Research Program Area: Neurology

Abstract

The larynx functions to regulate airflow and voice production in dogs. Paired muscles in the larynx (the dorsal cricoarytenoid muscles) open up the larynx during inspiration, decreasing resistance to airflow. These muscles are innervated by the caudal laryngeal nerves. Damage to or degeneration of the nerves produces laryngeal paralysis. Acquired laryngeal paralysis generally affects older, large breed dogs. These dogs have varying degrees of difficulty breathing because the larynx cannot open normally during inspiration, and often require surgical treatment to breathe adequately. In the vast majority of cases there is no obvious underlying cause found for the disease. Leonbergers suffer from a poorly understood inherited nerve degeneration disease that manifests initially as laryngeal paralysis. Laryngeal paralysis in humans is associated with a mutation in the gene coding for dynactin. Dynactin is a microtubule motor protein activator that is vital for transport of substances within nerves. Disruption of normal transport within nerves has been implicated in a number of diseases in people and is associated with late onset motor nerve disease in mice. These conditions bear a striking similarity to the disease in Leonbergers and idiopathic laryngeal paralysis in other breeds. Of these, preliminary study shows that Labrador Retrievers are at a significantly higher risk of developing laryngeal paralysis. The goals of this study are to sequence the dynactin gene in normal dogs and to evaluate Labrador Retrievers and Leonbergers affected with laryngeal paralysis for dynactin gene mutations.

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