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  • Author or Editor: Michael O'Grady x
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Objective—To identify a causative mutation for dilated cardiomyopathy (DCM) in Doberman Pinschers by sequencing the coding regions of 10 cardiac genes known to be associated with familial DCM in humans.

Animals—5 Doberman Pinschers with DCM and congestive heart failure and 5 control mixed-breed dogs that were euthanized or died.

Procedures—RNA was extracted from frozen ventricular myocardial samples from each dog, and first-strand cDNA was synthesized via reverse transcription, followed by PCR amplification with gene-specific primers. Ten cardiac genes were analyzed: cardiac actin, α-actinin, α-tropomyosin, β-myosin heavy chain, metavinculin, muscle LIM protein, myosinbinding protein C, tafazzin, titin-cap (telethonin), and troponin T. Sequences for DCM-affected and control dogs and the published canine genome were compared.

Results—None of the coding sequences yielded a common causative mutation among all Doberman Pinscher samples. However, 3 variants were identified in the α-actinin gene in the DCM-affected Doberman Pinschers. One of these variants, identified in 2 of the 5 Doberman Pinschers, resulted in an amino acid change in the rod-forming triple coiled-coil domain.

Conclusions and Clinical Relevance—Mutations in the coding regions of several genes associated with DCM in humans did not appear to consistently account for DCM in Doberman Pinschers. However, an α-actinin variant was detected in some Doberman Pinschers that may contribute to the development of DCM given its potential effect on the structure of this protein. Investigation of additional candidate gene coding and noncoding regions and further evaluation of the role of α-actinin in development of DCM in Doberman Pinschers are warranted.

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in American Journal of Veterinary Research


Characteristic alterations in the serum and urine biochemical profiles of Doberman Pinschers with congestive heart failure (chf) resulting from idiopathic dilated cardiomyopathy were determined. We compared these alterations with those observed in 2 other models of chf: rate overload induced by rapid ventricular pacing in dogs, and biventricular hypertrophy and dilatation induced in turkey poults by furazolidone toxicosis. Serum and urine biochemical changes in both models of chf in dogs were mild to moderate in degree, and were moderately consistent. They could be attributed to secondary neurohumoral, hepatic, and renal effects of heart failure. The most marked and consistent changes observed were mildly decreased anion gap that developed, in part, because of decreased serum sodium concentration, moderately increased catecholamine concentrations, moderate lactaciduria, hyposthenuria, and mildly increased urea concentrations and liver enzyme activities. In birds with furazolidone cardiomyopathy, we observed mild increases in serum urate concentration, liver and muscle enzyme activities, but moderately increased sodium concentration with decreased chloride concentration. In the pacing and furazolidone models, in which chf was rapidly induced, moderate to marked hypoproteinemia was attributable to decreases in albumin and globulin concentrations. Using the avian model we found that the hypoproteinemia could be largely attributed to blood volume expansion, and to a lesser extent, inanition. Development of hypoalbuminemia during rapid ventricular pacing and furazolidone treatment may contribute to the effects of rate overload or drug toxicity in the pathogenesis of chf, because hypoalbuminemia may contribute to altered hemodynamics and neuroendocrine system activation. Our data indicate that clinical biochemical analysis of serum and urine may be useful for assessing progression of chf.

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in American Journal of Veterinary Research


Objective—To evaluate the potential importance of dystrophin, α-sarcoglycan (adhalin), and β-dystroglycan, by use of western blot analysis, in several breeds of dogs with dilated cardiomyopathy.

Sample Population—Myocardial samples obtained from 12 dogs were evaluated, including tissues from 7 dogs affected with dilated cardiomyopathy, 4 control dogs with no identifiable heart disease (positive control), and 1 dog affected with Duchenne muscular dystrophy (negative control for dystrophin). Of the affected dogs, 4 breeds were represented (Doberman Pinscher, Dalmatian, Bullmastiff, and Irish Wolfhound).

Procedure—Western blot analysis was used for evaluation of myocardial samples obtained from dogs with and without dilated cardiomyopathy for the presence of dystrophin and 2 of its associated glycoproteins, α-sarcoglycan and β-dystroglycan.

Results—Detectable differences were not identified between dogs with and without myocardial disease in any of the proteins evaluated.

Conclusions and Clinical Relevance—Abnormalities in dystrophin, α-sarcoglycan, and β-dystroglycan proteins were not associated with the development of dilated cardiomyopathy in the dogs evaluated in this study. In humans, the development of molecular biological techniques has allowed for the identification of specific causes of dilated cardiomyopathy that were once considered to be idiopathic. The use of similar techniques in veterinary medicine may aid in the identification of the cause of idiopathic dilated cardiomyopathy in dogs, and may offer new avenues for therapeutic intervention. ( Am J Vet Res 2001;62:67–71)

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in American Journal of Veterinary Research