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Rescue of skeletal muscle -actin–null mice by cardiac (fetal) -actin

¹ Centre for Medical Research, ² Discipline of Physiology, School of Biomedical, Biomolecular, and Chemical Sciences, and ³ School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia
⁴ Western Australian Institute for Medical Research, Nedlands, Western Australia 6009, Australia
⁵ Medical Research Council Functional Genetics Unit and ⁶ Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 2JD, England, UK
⁷ PathWest Department of Cytogenetics, King Edward Memorial Hospital, Perth, Western Australia 6008, Australia
⁸ Department of Pathology and Immunology, University Medical Center, University of Geneva, 1211 Geneva 4, Switzerland
⁹ Wolfson Centre for Inherited Neuromuscular Diseases, Robert Jones and Agnes Hunt Orthopaedic and District Hospital, Oswestry SY10 7AG, England, UK
¹⁰ Department of Neuropathology and ¹¹ PathWest Department of Anatomical Pathology, Royal Perth Hospital, Perth, Western Australia 6001, Australia
¹² Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229

Correspondence to Kristen J. Nowak: knowak{at}cyllene.uwa.edu.au

Skeletal muscle -actin (ACTA1) is the major actin in postnatal skeletal muscle. Mutations of ACTA1 cause mostly fatal congenital myopathies. Cardiac -actin (ACTC) is the major striated actin in adult heart and fetal skeletal muscle. It is unknown why ACTC and ACTA1 expression switch during development. We investigated whether ACTC can replace ACTA1 in postnatal skeletal muscle. Two ACTC transgenic mouse lines were crossed with Acta1 knockout mice (which all die by 9 d after birth). Offspring resulting from the cross with the high expressing line survive to old age, and their skeletal muscles show no gross pathological features. The mice are not impaired on grip strength, rotarod, or locomotor activity. These findings indicate that ACTC is sufficiently similar to ACTA1 to produce adequate function in postnatal skeletal muscle. This raises the prospect that ACTC reactivation might provide a therapy for ACTA1 diseases. In addition, the mouse model will allow analysis of the precise functional differences between ACTA1 and ACTC.

Abbreviations used in this paper: EDL, extensor digitorum longus; HSA, human skeletal muscle -actin; KO, knockout; LC, liquid chromatography; MHC, myosin heavy chain; MRM, multiple reaction monitoring; MS, mass spectrometry.

© 2009 Nowak et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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