Human Molecular Genetics Advance Access originally published online on June 22, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 16 1775-1784
DOI: 10.1093/hmg/ddh190
Human Molecular Genetics, Vol. 13, No. 16 © Oxford University Press 2004; all rights reserved
Laminin 
1 chain reduces muscular dystrophy in laminin 2 chain deficient mice
1Department of Cell and Molecular Biology, Section for Cell and Developmental Biology, University of Lund, Lund, Sweden and 2Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
Received April 14, 2004; Accepted June 11, 2004
Laminin (LN) 
2 chain deficiency in humans and mice leads to severe forms of congenital muscular dystrophy (CMD). Here, we investigated whether LN1 chain in mice can compensate for the absence of LN2 chain and prevent the development of muscular dystrophy. We generated mice expressing a LN1 chain transgene in skeletal muscle of LN2 chain deficient mice. LN1 is not normally expressed in muscle, but the transgenically produced LN1 chain was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains (4, ß2). In 4-month-old mice, LN1 chain could fully prevent the development of muscular dystrophy in several muscles, and partially in others. The LN1 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 LN2 chain deficiency by LN1 chain may serve as a paradigm for gene therapy of CMD in patients.
* To whom correspondence should be addressed at: Department of Cell and Molecular Biology, Section for Cell and Developmental Biology, University of Lund, BMC B12, 221 84 Lund, Sweden. Tel: +46 462220812; Fax: +46 462220855; Email: madeleine.durbeej_hjalt{at}medkem.lu.se
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