Laminin {alpha}1 chain improves laminin {alpha}2 chain deficient peripheral neur

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Hum Mol Genet. 2006 Aug 7

Laminin {alpha}1 chain improves laminin {alpha}2 chain deficient

peripheral neuropathy.

Gawlik KI, Li JY, sen A, Durbeej M.

Muscle Biology Unit, Division for Cell and Matrix Biology, Department

of Experimental Medical Science, University of Lund, Lund, Sweden.

Absence of laminin alpha2 chain leads to a severe form of congenital

muscular dystrophy (MDC1A) associated with peripheral neuropathy.

Hence, future therapies should be aimed at alleviating both muscle

and neurological dysfunction. Pre-clinical studies in animal models

have mainly focused on ameliorating the muscle phenotype.

Here we show that transgenic expression of laminin alpha1 chain in

muscles and the peripheral nervous system of laminin alpha2 chain

deficient mice reduced muscular dystrophy and largely corrected the

peripheral nerve defects. The presence of laminin alpha1 chain in the

peripheral nervous system resulted in near normal myelination,

restored Schwann cell basement membranes and improved rotarod

performance.

In summary, we postulate that laminin alpha1 chain is an excellent

substitute for laminin alpha2 chain in multiple tissues and suggest

that treatment with laminin alpha1 chain may be beneficial for MDC1A

in humans.