Dilated Cardiomyopathy of Doberman Pinschers: Retrospective Histomorphologic Evaluation of Heart from 32 Cases

Everett, Rosie; McGann, Judeth K.; Wimberly, Hallie; Althoff, J.

doi:10.1354/vp.36-3-221

Cited by 25 publications

(23 citation statements)

References 12 publications

(9 reference statements)

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“…The robustness of these results was not affected by the inclusion of additional covariates such as birth year, birth month, country of origin and inbreeding coefficient. In accordance with previous reports, we found a higher prevalence of DCM in male dogs (Calvert et al, 1982;Harpster, 1991;Everett et al, 1999;Vollmar, 2000). Furthermore, our analysis showed different genotypic distributions among male and female dogs.…”

Section: Discussionsupporting

confidence: 92%

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Complex segregation analysis of dilated cardiomyopathy (DCM) in Irish wolfhounds

Distl

Vollmar²,

Broschk

et al. 2007

Heredity

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The objective of the present study was to analyse the mode of inheritance for dilated cardiomyopathy (DCM) in Irish wolfhounds using regressive logistic models by testing for mechanisms of genetic transmission. Insights from this spontaneous animal model should aid importantly in understanding basic pathogenic mechanisms with regard to genetics and molecular biology of DCM in humans. Moreover, a procedure for the simultaneous prediction of breeding values and the estimation of genotype probabilities for DCM is expected to markedly improve breeding programmes. Results of cardiovascular examinations of 1018 dogs carried out between 1987 and 2003 by one veterinarian were analysed. Data of 878 dogs from 531 litters in 147 different kennels were used for complex segregation analyses. Pedigree information was available for more than 15 generations. Male dogs were affected significantly more often by DCM than female dogs. The segregation analysis showed that among all other tested models a mixed monogenic-polygenic model including a sex-dependent allele effect best explained the segregation of affected animals in the pedigrees. A pure monogenic inheritance of DCM could be significantly rejected in favour of the major gene and most general model. The gene action of the major gene was significantly different between female and male dogs.

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Section: Discussionsupporting

confidence: 92%

“…Characteristically, clinical signs of DCM are manifested between 4 and 10 years of age, although juvenile forms leading to rapid death are occasionally recognized Sleeper et al, 2002;Vollmar et al, 2003). Males appear to be more commonly affected than females (Calvert et al, 1982;Harpster, 1991;Everett et al, 1999;Vollmar, 2000).…”

Section: Introductionmentioning

confidence: 99%

Complex segregation analysis of dilated cardiomyopathy (DCM) in Irish wolfhounds

Distl

Vollmar²,

Broschk

et al. 2007

Heredity

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“…The turkey (29 -31), cat (32)(33)(34), and dog (35)(36)(37) all exhibit a high instance of inherited DCM. Although the monkey heart has not been extensively studied, it is worth noting that spontaneous cardiomyopathies in pig and monkey have been documented (38,39).…”

Section: The Correlation Of Aberrant Ctnt Splicing With Dilatedmentioning

confidence: 99%

“…Although the TnT-4 expression in human cTnT (11,14,15) could be secondary and compensatory to the heart failure conditions, it lends support to the role of the cTnT NH 2 -terminal variation in modulating myocardial function. The aberrant splicing of exon 8 in turkey cTnT and exons 5 and 7 or 6 in dog and guinea pig cTnT occurs as primary changes, indicating a cause or precondition for the development of DCM and heart failure in these animals (13,(32)(33)(34)(35)(36)(37). With the much larger structural and functional changes resulting from the abnormal splicing of exons 5 (11) and 7 (13), the cat and dog cTnT variants are likely to have greater functional effects than the human TnT-4.…”

Section: The Correlation Of Aberrant Ctnt Splicing With Dilatedmentioning

confidence: 99%

Cardiac Troponin T Variants Produced by Aberrant Splicing of Multiple Exons in Animals with High Instances of Dilated Cardiomyopathy

Biesiadecki

Elder

et al. 2002

Journal of Biological Chemistry

100

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Adult cardiac muscle normally expresses a single cardiac troponin T (cTnT). As a potential pathogenic mechanism for turkey dilated cardiomyopathy, the splice-out of a normally constitutive exon generates an additional low molecular weight cTnT with altered conformation and function. We further found that aberrant splicing of cTnT also occurs in several mammals correlating to dilated cardiomyopathy. Skipping of the same exon as that in the turkey was found in the canine cTnT. Spliceout of the adjacent exon 6 occurred in the guinea pig cTnT. Retention of the embryonic exon 5 was found in the cTnT of cat, dog, and guinea pig. These aberrant splicing variants significantly altered the structure of cTnT to sustain functional effects as that in the myopathic turkey cTnT. The genomic sequence of canine cTnT gene shows no specific alterations. However, the alternative splicing patterns of canine cTnT are different in developing cardiac and skeletal muscles, suggesting abnormality of trans-regulatory factors. Transgenic expression of the aberrant cTnT variants resulted in contractile changes in mouse cardiomyocytes. The findings support the hypothesis that thin filament heterogeneity due to the co-expression of alternatively spliced cTnT variants may desynchronize myocardial contraction and contribute to the pathogenesis and pathophysiology of cardiomyopathy and heart failure.

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“…44 The attenuated wavy fiber form of DCM has been described in medium-to giant-breed dogs, 40,42,45 and specifically in Newfoundland dogs, 43 PWDs, 14 and 3 Doberman Pinscher littermates. 49 The fatty infiltration-degenerative form predominates in Doberman Pinschers with DCM 19 and Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). 3 Irrespective of the histologic type, the underlying cause in most cases of canine DCM remains undetermined.…”

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confidence: 99%

Histological Characterization of Dilated Cardiomyopathy in the Juvenile Toy Manchester Terrier

et al. 2013

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Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy in the dog, most often occurs in certain breeds. The objective of this study was to describe a rapidly progressive form of DCM that has been recently recognized in juvenile Toy Manchester Terrier dogs (TMTs). The clinical history and gross findings were reviewed in a group of 14 TMTs, and histologic sections of heart were examined in 12 of those 14 TMTs with DCM. Histochemical and histomorphometric analyses were employed to compare the heart in TMTs affected by DCM with that of control dogs. TMTs ranged in age from 10 to 58.3 weeks, with males and females being equally affected. Affected TMT hearts contained foci of degeneration and loss of myofibers with fibrosis and mild lymphoplasmacytic infiltrates. Less prominent features included foci of acute myofiber degeneration and necrosis with or without intralesional mineralization and mild to moderate suppurative and lymphoplasmacytic infiltrates. Morphometric quantification demonstrated that the right ventricle was more severely affected (P .05) than the left ventricle with variable involvement of the interventricular septum. Immunohistochemistry for canine parvovirus was negative in all heart samples. However, the absence of parvoviral antigen does not rule out a possible viral or autoimmune cause. The presence of these myocardial lesions among closely related dogs suggests a genetic contribution to this disease process in the TMT.

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Dilated Cardiomyopathy of Doberman Pinschers: Retrospective Histomorphologic Evaluation of Heart from 32 Cases

Cited by 25 publications

References 12 publications

Complex segregation analysis of dilated cardiomyopathy (DCM) in Irish wolfhounds

Complex segregation analysis of dilated cardiomyopathy (DCM) in Irish wolfhounds

Cardiac Troponin T Variants Produced by Aberrant Splicing of Multiple Exons in Animals with High Instances of Dilated Cardiomyopathy

Histological Characterization of Dilated Cardiomyopathy in the Juvenile Toy Manchester Terrier

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