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Lookup NU author(s): Dr Ingrid Verhaart
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Duchenne muscular dystrophy is caused by mutations that prevent synthesis of functional dystrophin. All patients develop dilated cardiomyopathy. Promising therapeutic approaches are underway that successfully restore dystrophin expression in skeletal muscle. However, their efﬁciency in the heart is limited. Improved quality and function of only skeletal muscle potentially accelerate the development of cardiomyopathy. Our study aimed to elucidate which dystrophin levels in the heart are required to prevent or delay cardiomyopathy in mice. Heart function and pathology assessed with magnetic resonance imaging and histopathological analysis were compared between 2, 6 and 10-month-old female mdx-XistΔhs mice, expressing low dystrophin levels (3–15%) in a mosaic manner based on skewed X-inactivation, dystrophin-negative mdx mice, and wild type mice of corresponding genetic backgrounds and gender.With age mdx mice developed dilated cardiomyopathy and hypertrophy, whereas the onset of heart pathology was delayed and function improved in mdx-XistΔhs mice. The ejection fraction, the most severely affected parameter for both ventricles, correlated to dystrophin expression and the percentage of ﬁbrosis. Fibrosis was partly reduced from 9.8% in mdx to 5.4% in 10 month old mdx-XistΔhs mice. These data suggest that mosaic expression of 4–15% dystrophin in the heart is sufﬁcient to delay the onset and ameliorate cardiomyopathy in mice.
Author(s): van Putten M, van der Pijl EM, Hulsker M, Verhaart IE, Nadarajah VD, van der Weerd L, Aartsma-Rus A
Publication type: Article
Publication status: Published
Journal: Journal of Molecular and Cellular Cardiology
Print publication date: 01/04/2014
Online publication date: 29/01/2014
Acceptance date: 21/01/2014
Date deposited: 12/07/2016
ISSN (print): 0022-2828
ISSN (electronic): 1095-8584
PubMed id: 24486194
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