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Principal Investigator: Dr. Sydney Moise
Contact Information: E-mail: nsm2@cornell.edu - Phone: 607-253-3029
Sponsor: Morris Animal Foundation
Grant Number: D06CA-059
Title: Altered Intercellular Communications, Arrhythmias, and Sudden Death of Boxer Dogs
Annual Direct Cost: $23,203
Project Period: 09/01/06-08/31/09
DESCRIPTION (provided by applicant): Boxer dogs are commonly afflicted with arrhythmogenic right ventricular cardiomyopathy (ARVC) (previously Boxer Cardiomyopathy), an inherited myocardial disease causing a high incidence of arrhythmias, heart failure and death. Hearts of afflicted dogs are infiltrated with a fibrofatty infiltrate. We have preliminary results demonstrating abnormal structure of the intercalated disc (ID) in afflicted boxers. Our results are similar to those seen in humans and mice with ARVC in which mutations in the genes coding for proteins in the desmosome (a component of the ID) have been identified. Disease of the desmosome results in poor mechanical and electrical coupling which can be responsible for the clinical syndrome. We propose to examine the hearts of afflicted boxers by immunofluorescence, electron microscopy, and Western blotting to determine if our preliminary results are consistent with regard to the protein expression of Cx43, plakoglobin, desmoplakin, plakophilin-2, desmin and cadherin. From these data we will then selectively sequence the genes coding for these proteins to search for a mutation. We are optimistic about our ability to find the mutation because mutations in the desmosomal coding genes have been identified in both humans and mice with ARVC and our preliminary data support this confidence.
Statement of Research Problem and Objectives. A common heart disease in the boxer causes abnormal heart beats, fainting, heart failure, and death. We believe a gene mutation that prevents the cells of the heart from communicating properly is responsible. Our study will look at the protein expression in hearts of dogs that die. A similar disease is seen in people. In people the mutations are known. We will test to see if the mutation is the same in the boxer.
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