Laminin α1 chain reduces muscular dystrophy in laminin α2 chain deficient mice

被引:110
作者
Gawlik, K
Miyagoe-Suzuki, Y
Ekblom, P
Takeda, S
Durbeej, M
机构
[1] Lund Univ, Dept Cell & Mol Biol, Sect Cell & Dev Biol, S-22184 Lund, Sweden
[2] Natl Inst Neurosci, Dept Mol Therapy, Natl Ctr Neurol & Psychiat, Tokyo, Japan
关键词
D O I
10.1093/hmg/ddh190
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Laminin (LN) alpha2 chain deficiency in humans and mice leads to severe forms of congenital muscular dystrophy (CMD). Here, we investigated whether LNalpha1 chain in mice can compensate for the absence of LNalpha2 chain and prevent the development of muscular dystrophy. We generated mice expressing a LNalpha1 chain transgene in skeletal muscle of LNalpha2 chain deficient mice. LNalpha1 is not normally expressed in muscle, but the transgenically produced LNalpha1 chain was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains (alpha4, beta2). In 4-month-old mice, LNalpha1 chain could fully prevent the development of muscular dystrophy in several muscles, and partially in others. The LNalpha1 chain transgene not only reversed the appearance of histopathological features of the disease to a remarkable degree, but also greatly improved health and longevity of the mice. Correction of LNalpha2 chain deficiency by LNalpha1 chain may serve as a paradigm for gene therapy of CMD in patients.
引用
收藏
页码:1775 / 1784
页数:10
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