Laminins and human disease

The laminin protein family has diverse tissue expression patterns and is in volved in the pathology of a number of organs, including skin, muscle, and nerve. In the skin, laminins 5 and 6 contribute to dermal-epidermal cohesio n, and mutations in the constituent chains result in the blistering phenoty pe observed in patients with junctional epidermolysis bullosa (JEB). Alleli c heterogeneity is observed in patients with JEB: mutations that results in premature stop codons produce a more severe phenotype than do missense mut ations. Gene therapy approaches are currently being studied in the treatmen t of this disease. A blistering phenotype is also observed in patients with acquired cicatricial pemphigoid (CP). Autoantibodies targeted against lami nins 5 and 6 destabilize epithelial adhesion and are pathogenic. In muscle cells, laminin alpha2 is a component of the bridge that links the actin cyt oskeleton to the extracellular matrix. In patients with laminin alpha2 muta tions, the bridge is disrupted and mature muscle cells apoptose. Congenital muscular dystrophy (CMD) results. The role of laminin in diseases of the n ervous system is less well defined, but the extracellular protein has been shown to serve an important role in peripheral nerve regeneration. The adhe sive molecule influences neurite outgrowth, neural differentiation, and syn apse formation. The broad spatial distribution of laminin gene products sug gests that laminin may be involved in a number of diseases for which pathog enic mechanisms are still being unraveled. Microsc. Res. Tech. 51:262-279, 2000. (C) 2000 Wiley-Liss. Inc.