Nowak Kristen J, Ravenscroft Gianina, Jackaman Connie, Filipovska Aleksandra, Davies Stefan M, Lim Esther M, Squire Sarah E, Potter Allyson C, Baker Elizabeth, Clément Sophie, Sewry Caroline A, Fabian Victoria, Crawford Kelly, Lessard James L, Griffiths Lisa M, Papadimitriou John M, Shen Yun, Morahan Grant, Bakker Anthony J, Davies Kay E, Laing Nigel G
Centre for Medical Research, School of Biomedical, Biomolecular, and Chemical Sciences, The University of Western Australia, Perth, Western Australia 6009, Australia.
J Cell Biol. 2009 Jun 1;185(5):903-15. doi: 10.1083/jcb.200812132. Epub 2009 May 25.
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.
骨骼肌α-肌动蛋白（ACTA1）是出生后骨骼肌中的主要肌动蛋白。ACTA1突变大多会导致致命的先天性肌病。心肌α-肌动蛋白（ACTC）是成人心肌和胎儿骨骼肌中的主要横纹肌动蛋白。目前尚不清楚为何ACTC和ACTA1的表达在发育过程中会发生转换。我们研究了ACTC是否能在出生后的骨骼肌中替代ACTA1。将两个ACTC转基因小鼠品系与Acta1基因敲除小鼠（所有这些小鼠在出生后9天内死亡）进行杂交。与高表达品系杂交产生的后代能存活至老年，并且它们的骨骼肌没有明显的病理特征。这些小鼠在握力、转棒试验或运动活动方面没有受损。这些发现表明ACTC与ACTA1足够相似，能够在出生后的骨骼肌中发挥充分的功能。这增加了ACTC重新激活可能为ACTA1疾病提供治疗方法的前景。此外，该小鼠模型将有助于分析ACTA1和ACTC之间精确的功能差异。
