Dilated cardiomyopathy(DCM) is a primary heart muscle disease characterized by systolic dysfunction and ventricular dilatation; it occurs naturally in many species.(1-3) Approximately 20% of human DCM appears to be of familial origin, and the trait may be inherited in an autosomal (dominant or recessive), X-linked, or mitochondrial pattern.(4,5) Canine models of familial DCM also exists. Greater than 50% of dogs diagnosed as having DCM are Doberman pinschers and they have close similarities to familial DCM in humans. (6-8) Golden retrievers are also known to have familial DCM and sometimes have DCM associated with a muscular dystrophy similar to Duchenne muscular dystrophy (DMD) in humans.(9-12) In addition to DCM, dystrophin abnormalities have been shown in some cases. (13-15) We believe that a natural animal model of familial DCM could provide opportunities to study at least one cause of DCM at the molecular level and provide a candidate gene model for human disease. Pedigrees from Doberman pinschers and golden retrievers with DCM have been collected; the phenotypes of affected and unaffected individuals were characterized. Blood samples have also been obtained from affected and unaffected family members to develop lymphoblastoid cell lines as an immortalized.source of DNA, and for DNA isolation. Those dogs succumbing to DCM will be autopsied; cardiac and skeletal muscle samples have been obtained (fresh frozen when possible, or formalin-fixed). Doberman pinscher and golden retriever DNA isolated from individuals (blood, tissue) will be subjected to linkage analysis to map the chromosomal locus responsible for DCM and the region will be cloned to isolate and identify the responsible gene prior to performing mutation analysis. Also, samples will be analyzed for dystrophin deletions by multiplex PCR and other mutations.(16,17) This study will ultimately provide a natural animal model in which to study familial DCM at a molecular level and potentially provide a candidate gene(s) for evaluation in humans with this form of cardiomyopathy, as well as potentially improving the knowledge of DCM in DMD and X-linked DCM, human diseases due to dystrophin abnormalities.(18)

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003236-04
Application #
2451975
Study Section
Special Emphasis Panel (ZHL1-CCT-L (O1))
Project Start
1995-05-18
Project End
2000-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210