AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice
Heckmann MB, Bauer R, Jungmann A, Winter L, Rapti K, Strucksberg KH, Clemen CS, Li Z, Schroeder R, Katus HA, Mueller OJ (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 23
Pages Range: 673-9
Journal Issue: 8-9
DOI: 10.1038/gt.2016.40
Abstract
Mutations of the human desmin (DES) gene cause autosomal dominant and recessive myopathies affecting skeletal and cardiac muscle tissue. Desmin knockout mice (DES-KO), which develop progressive myopathy and cardiomyopathy, mirror rare human recessive desminopathies in which mutations on both DES alleles lead to a complete ablation of desmin protein expression. Here, we investigated whether an adeno-associated virus-mediated gene transfer of wild-type desmin cDNA (AAV-DES) attenuates cardiomyopathy in these mice. Our approach leads to a partial reconstitution of desmin protein expression and the de novo formation of the extrasarcomeric desmin-syncoilin network in cardiomyocytes of treated animals. This finding was accompanied by reduced fibrosis and heart weights and improved systolic left-ventricular function when compared with control vector-treated DES-KO mice. Since the re-expression of desmin protein in cardiomyocytes of DES-KO mice restores the extrasarcomeric desmin-syncoilin cytoskeleton, attenuates the degree of cardiac hypertrophy and fibrosis, and improves contractile function, AAV-mediated desmin gene transfer may be a novel and promising therapeutic approach for patients with cardiomyopathy due to the complete lack of desmin protein expression.
Involved external institutions
Universitätsklinikum Heidelberg
Germany (DE)
University of Paris 6 - Pierre et Marie Curie / Université Paris VI Pierre et Marie Curie (UPMC)
France (FR)
Universität zu Köln
Germany (DE)
Germany (DE)
University of Paris 6 - Pierre et Marie Curie / Université Paris VI Pierre et Marie Curie (UPMC)
France (FR)
Universität zu Köln
Germany (DE)
How to cite
APA:
Heckmann, M.B., Bauer, R., Jungmann, A., Winter, L., Rapti, K., Strucksberg, K.-H.,... Mueller, O.J. (2016). AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice. Gene Therapy, 23(8-9), 673-9. https://doi.org/10.1038/gt.2016.40
MLA:
Heckmann, M. B., et al. "AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice." Gene Therapy 23.8-9 (2016): 673-9.
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