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

Kristen Nowak, Gina Ravenscroft, Connie Jackaman, Aleksandra Filipovska, Stefan Davies, Esther Lim, S.E. Squire, A.C. Potter, E. Baker, S. Clement, C.A. Sewry, V. Fabian, K. Crawford, J.L. Lessard, L.M. Griffiths, J.M. Papadimitriou, Yun Shen, Grant Morahan, Tony Bakker, K.E. DaviesNigel Laing

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Skeletal muscle α-actin (ACTA1) is the major actin in postnatal skeletal muscle. Mutations of ACTA1 cause mostly fatal congenital myopathies. Cardiac α-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.
Original languageEnglish
Pages (from-to)903-915
JournalThe Journal of Cell Biology
Volume185
Issue number5
DOIs
Publication statusPublished - 2009

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