Laminin {alpha}1 chain reduces muscular dystrophy in laminin {alpha}2 chain deficient mice.

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Abstract

Laminin (LN) {alpha}2 chain deficiency in humans and mice leads to severe forms of congenital muscular dystrophy (CMD). Here, we investigated whether LN{alpha}1 chain in mice can compensate for the absence of LN{alpha}2 chain and prevent the development of muscular dystrophy. We generated mice expressing a LN{alpha}1 chain transgene in skeletal muscle of LN{alpha}2 chain deficient mice. LN{alpha}1 is not normally expressed in muscle, but the transgenically produced LN{alpha}1 chain was incorporated into muscle basement membranes, and normalized the compensatory changes of expression of certain other laminin chains ({alpha}4, ß2). In 4-month-old mice, LN{alpha}1 chain could fully prevent the development of muscular dystrophy in several muscles, and partially in others. The LN{alpha}1 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 LN{alpha}2 chain deficiency by LN{alpha}1 chain may serve as a paradigm for gene therapy of CMD in patients.

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  • Medical Genetics
Original languageEnglish
Pages (from-to)1775-1784
JournalHuman Molecular Genetics
Volume13
Issue number16
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes