Universität zu Köln

Heckmann, M. B., Bauer, R., Jungmann, A., Winter, L., Rapti, K., Strucksberg, K-H, Clemen, C. S., Li, Z., Schroeder, R., Katus, H. A. and Mueller, O. J. (2016). AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice. Gene Ther., 23 (8-9). S. 673 - 680. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5462

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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 desminsyncoilin 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heckmann, M. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jungmann, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Winter, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rapti, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Strucksberg, K-H UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, C. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Katus, H. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, O. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-268006
DOI:	10.1038/gt.2016.40
Journal or Publication Title:	Gene Ther.
Volume:	23
Number:	8-9
Page Range:	S. 673 - 680
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5462
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MDX MICE; MUSCULAR-DYSTROPHY; LACKING DESMIN; MUSCLE; VECTORS; SKELETAL; EXPRESSION; HYPERTROPHY; PREVENTION; INJECTION Multiple languages Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26800