Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ): electrocardiographic, echocardiographic, and morphologic studies

Yugeta, Naoko; Urasawa, Nobuyuki; Fujii, Yoko; Yoshimura, M; Yuasa, Katsutoshi; Wada, Mitsuru; Nakura, Masao; Shimatsu, Yoshiki; Tomohiro, Masayuki; Takahashi, Akio; Motomura, Noboru; Wakao, Yoshito; Nakamura, Akinori; Takeda, Shin’ichi

doi:10.1186/1471-2261-6-47

Cited by 58 publications

(77 citation statements)

References 36 publications

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“…12 Beagle-based dystrophic dogs show mild phenotypes not only in skeletal muscle 13 but also in cardiac muscle. 14 Moreover, we found that the distinctive deep Q waves precede the LV posterobasal lesion on echocardiography and histopathology in CXMD J . 14 The histopathological changes in the conduction system have not been investigated fully, especially in the early stages of the disease, although the expressions of dystrophin and DAPs have been examined in normal systems.…”

Section: Clinical Perspective P 2448mentioning

confidence: 87%

“…14 Moreover, we found that the distinctive deep Q waves precede the LV posterobasal lesion on echocardiography and histopathology in CXMD J . 14 The histopathological changes in the conduction system have not been investigated fully, especially in the early stages of the disease, although the expressions of dystrophin and DAPs have been examined in normal systems. [15][16][17][18] The molecular mechanisms of the dystrophin-deficient heart are still unclear.…”

Section: Clinical Perspective P 2448mentioning

confidence: 87%

“…The phenotype of these affected dogs has been described previously. 13,14 All experimental animals were part of the CXMD J breeding colony at the General Animal Research Facility, National Institute of Neuroscience, National Center of Neurology and Psychiatry (Tokyo, Japan) 12 …”

Section: Animalsmentioning

confidence: 99%

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Selective Vacuolar Degeneration in Dystrophin-Deficient Canine Purkinje Fibers Despite Preservation of Dystrophin-Associated Proteins With Overexpression of Dp71

et al. 2008

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Background-Respiratory support therapy significantly improves life span in patients with Duchenne muscular dystrophy; cardiac-related fatalities, including lethal arrhythmias, then become a crucial issue. It is therefore important to more thoroughly understand cardiac involvement, especially pathology of the conduction system, in the larger Duchenne muscular dystrophy animal models such as dystrophic dogs. Methods and Results-When 10 dogs with canine X-linked muscular dystrophy in Japan (CXMD J ) were examined at the age of 1 to 13 months, dystrophic changes of the ventricular myocardium were not evident; however, Purkinje fibers showed remarkable vacuolar degeneration as early as 4 months of age. The degeneration of CXMD J Purkinje fibers was coincident with overexpression of Dp71 at the sarcolemma and translocation of -calpain to the cell periphery near the sarcolemma or in the vacuoles. Immunoblotting of the microdissected fraction showed that -calpain-sensitive proteins such as desmin and cardiac troponin-I or -T were selectively degraded in the CXMD J Purkinje fibers. Utrophin was highly upregulated in the earlier stage of CXMD J Purkinje fibers, but the expression was dislocated when vacuolar degeneration was recognized at 4 months of age. Nevertheless, the expression of dystrophin-associated proteins ␣-, ␤-, ␥-, and ␦-sarcoglycans and ␤-dystroglycan was well maintained at the sarcolemma of Purkinje fibers. Conclusions-Selective vacuolar degeneration of Purkinje fibers was found in the early stages of dystrophin deficiency.Dislocation of utrophin besides upregulation of Dp71 can be involved with this pathology. The degeneration of Purkinje fibers can be associated with the distinct deep Q waves in ECG and fatal arrhythmia seen in dystrophin deficiency.

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Section: Clinical Perspective P 2448mentioning

confidence: 87%

Section: Clinical Perspective P 2448mentioning

confidence: 87%

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Selective Vacuolar Degeneration in Dystrophin-Deficient Canine Purkinje Fibers Despite Preservation of Dystrophin-Associated Proteins With Overexpression of Dp71

et al. 2008

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“…CXMD dog models show longer life span due to slower progression of muscle wasting compared to GRMD dogs (Willmann et al, 2009). Progress of cardiomyopathy in the CXMD dog is also milder than in GRMD (Yugeta et al, 2006).…”

Section: Canine Muscular Dystrophy Modelmentioning

confidence: 93%

Genetic Therapy for Duchenne Muscular Dystrophy: Principles and Progress

Koo¹,

Popplewell²,

Malerba³

et al. 2012

Muscular Dystrophy

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“…Sinais clínicos de insuficiência cardíaca congestiva só são verificados em período próximo à morte (Moise et al 1991, Chetboul et al 2004, Pellegrino et al 2007. O eletrocardiograma (ECG) pode apresentar-se distintamente anormal em pacientes com distrofia muscular de Duchenne (Moise et al 1991, Pacioretty et al 1994, Yugeta et al 2006.…”

Section: Introductionunclassified

Padronização de parâmetros eletrocardiográficos de cães da raça Golden Retriever clinicamente sadios

et al. 2010

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ABSTRACT.-Pellegrino A., Yamaki F.L., Pereira R.C., Oliveira V. The Duchenne's muscular dystrophy (DMD) in humans is a X-linked neuromuscular disease, of recessive character, caused either by the absence or dysfunction of the dystrophin. Clinically, it is characterized by severe alteration in the skeletal musculature, resulting in precocious death. In Golden Retriever dogs, the mutation that takes to the muscular dystrophy happens spontaneously and the extensive homology among the pathogenesis of DMD and of Golden Retriever muscular dystrophy allows to qualify the dog as the main substitute of humans in the clinical tests of new therapies. The deficient myocardium in distrofin is more vulnerable to the pressure overload and the patients with DMD can develop dilated cardiomyopathy, arterial hypertension and the electrocardiogram can come distinctly abnormal. In the present study, 38 healthy Golden Retriever dogs were evaluated by electrocardiographic exam with the purpose to obtain parameters for the standardization of the electrocardiogram in the referred breed, what hereafter can serve as reference in the identification of bearer or affected dogs. Electrocardiographic values obtained were within normal values and reference for the various breeds of dogs, and the variables weight and age significantly altered heart rate and amplitude of the QRS complex.

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Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ): electrocardiographic, echocardiographic, and morphologic studies

Cited by 58 publications

References 36 publications

Selective Vacuolar Degeneration in Dystrophin-Deficient Canine Purkinje Fibers Despite Preservation of Dystrophin-Associated Proteins With Overexpression of Dp71

Selective Vacuolar Degeneration in Dystrophin-Deficient Canine Purkinje Fibers Despite Preservation of Dystrophin-Associated Proteins With Overexpression of Dp71

Genetic Therapy for Duchenne Muscular Dystrophy: Principles and Progress

Padronização de parâmetros eletrocardiográficos de cães da raça Golden Retriever clinicamente sadios

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