Decreased triadin and increased calstabin2 expression in Great Danes with dilated cardiomyopathy.
BACKGROUND
Dilated cardiomyopathy (DCM) is a common cardiac disease of Great Dane dogs, yet very little is known about the underlying molecular abnormalities that contribute to disease.


OBJECTIVE
Discover a set of genes that are differentially expressed in Great Dane dogs with DCM as a way to identify candidate genes for further study as well as to better understand the molecular abnormalities that underlie the disease.


METHODS
Three Great Dane dogs with end-stage DCM and 3 large breed control dogs.


METHODS
Prospective study. Transcriptional activity of 42,869 canine DNA sequences was determined with a canine-specific oligonucleotide microarray. Genome expression patterns of left ventricular tissue samples from affected Great Dane dogs were evaluated by measuring the relative amount of complementary RNA hybridization to the microarray probes and comparing it with expression from large breed dogs with noncardiac disease.


RESULTS
Three hundred and twenty-three transcripts were differentially expressed (> or = 2-fold change). The transcript with the greatest degree of upregulation (+61.3-fold) was calstabin2 (FKBP12.6), whereas the transcript with the greatest degree of downregulation (-9.07-fold) was triadin. Calstabin2 and triadin are both regulatory components of the cardiac ryanodine receptor (RyR2) and are critical to normal intracellular Ca2+ release and excitation-contraction coupling.


CONCLUSIONS
Great Dane dogs with DCM demonstrate abnormal calstabin2 and triadin expression. These changes likely affect Ca2+ flux within cardiac cells and may contribute to the pathophysiology of disease. Microarray-based analysis identifies calstabin2, triadin, and RyR2 function as targets of future study.
Oyama
M A
MA
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. maoyama@vet.upenn.edu
Chittur
S V
SV
Reynolds
C A
CA
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000662:veterinary; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000662:veterinary; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
D002352:Carrier Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C070048:triadin; D022021:Tacrolimus Binding Proteins