title: Rescue of skeletal muscle alpha-actin-null mice by cardiac (fetal) alpha-actin.
abstract: Skeletal muscle alpha-actin (ACTA1) is the major actin in postnatal skeletal muscle. Mutations of ACTA1 cause mostly fatal congenital myopathies. Cardiac alpha-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.
authors.affiliation: Centre for Medical Research, School of Biomedical, Biomolecular, and Chemical Sciences, The University of Western Australia, Perth, Western Australia 6009, Australia. knowak@cyllene.uwa.edu.au
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nowak
authors.forename: Gianina
authors.initials: G
authors.lastname: Ravenscroft
authors.forename: Connie
authors.initials: C
authors.lastname: Jackaman
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Filipovska
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Davies
authors.forename: Esther M
authors.initials: EM
authors.lastname: Lim
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Squire
authors.forename: Allyson C
authors.initials: AC
authors.lastname: Potter
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Baker
authors.forename: Sophie
authors.initials: S
authors.lastname: Clément
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.forename: Victoria
authors.initials: V
authors.lastname: Fabian
authors.forename: Kelly
authors.initials: K
authors.lastname: Crawford
authors.forename: James L
authors.initials: JL
authors.lastname: Lessard
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Griffiths
authors.forename: John M
authors.initials: JM
authors.lastname: Papadimitriou
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bakker
authors.forename: Kay E
authors.initials: KE
authors.lastname: Davies
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Laing
mesh_terms: D000199:Actins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D020869:Gene Expression Profiling; D006321:Heart / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000502:physiology
chemical_list: D000199:Actins; D020033:Protein Isoforms