Rescue of skeletal muscle alpha-actin-null mice by cardiac (fetal) alpha-actin.
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.
Nowak
Kristen J
KJ
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
Ravenscroft
Gianina
G
Jackaman
Connie
C
Filipovska
Aleksandra
A
Davies
Stefan M
SM
Lim
Esther M
EM
Squire
Sarah E
SE
Potter
Allyson C
AC
Baker
Elizabeth
E
Clément
Sophie
S
Sewry
Caroline A
CA
Fabian
Victoria
V
Crawford
Kelly
K
Lessard
James L
JL
Griffiths
Lisa M
LM
Papadimitriou
John M
JM
Shen
Yun
Y
Morahan
Grant
G
Bakker
Anthony J
AJ
Davies
Kay E
KE
Laing
Nigel G
NG
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
D000199:Actins; D020033:Protein Isoforms