Peripheral nerve involvement in merosin-deficient congenital muscular dystrophy and dy mouse.

Merosin, also called laminin-2, is an isoform of laminin comprised of the alpha 2, beta 1 and gamma 1 chains. Deficiency of merosin alpha 2 chain was recently identified as the primary cause of the classical form of congenital muscular dystrophy (CMD), an autosomal recessive neuromuscular disorder characterised by muscular dystrophy and brain white matter abnormalities. Interestingly, merosin-deficient CMD and its animal model dy mouse are also accompanied by dysmyelination of peripheral motor nerves. In peripheral nerve, merosin is expressed in the endoneurium surrounding the Schwann cell/myelin sheath, while the putative merosin receptors dystroglycan and alpha 6 beta 4 integrin are expressed in the outer membrane of Schwann cell/myelin sheath. Together with the well known fact that the deposition of laminin in the basement membrane is essential for Schwann cell myelination, these findings indicate that the interaction of merosin with dystroglycan and/or alpha 6 beta 4 integrin plays an important role in peripheral myelinogenesis and that the disturbance of this interaction leads to peripheral dysmyelination in merosin deficiency. The clinical significance of peripheral dysmyelination in merosin deficiency is also discussed.