Keratinocyte-targeted expression of human laminin ?2 rescues skin blistering and early lethality of laminin ?2 deficient mice. PloS one Adair-Kirk, T. L., Griffin, G. L., Meyer, M. J., Kelley, D. G., Miner, J. H., Keene, D. R., Marinkovich, M. P., Ruppert, J. M., Uitto, J., Senior, R. M. 2012; 7 (9)


Laminin-332 is a heterotrimeric basement membrane component comprised of the a3, ß3, and ?2 laminin chains. Laminin-332 modulates epithelial cell processes, such as adhesion, migration, and differentiation and is prominent in many embryonic and adult tissues. In skin, laminin-332 is secreted by keratinocytes and is a key component of hemidesmosomes connecting the keratinocytes to the underlying dermis. In mice, lack of expression of any of the three Laminin-332 chains result in impaired anchorage and detachment of the epidermis, similar to that seen in human junctional epidermolysis bullosa, and death occurs within a few days after birth. To bypass the early lethality of laminin-332 deficiency caused by the knockout of the mouse laminin ?2 chain, we expressed a dox-controllable human laminin ?2 transgene under a keratinocyte-specific promoter on the laminin ?2 (Lamc2) knockout background. These mice appear similar to their wild-type littermates, do not develop skin blisters, are fertile, and survive >1.5 years. Immunofluorescence analyses of the skin showed that human laminin ?2 colocalized with mouse laminin a3 and ß3 in the basement membrane zone underlying the epidermis. Furthermore, the presence of "humanized" laminin-332 in the epidermal basement membrane zone rescued the alterations in the deposition of hemidesmosomal components, such as plectin, collagen type XVII/BP180, and integrin a6 and ß4 chains, seen in conventional Lamc2 knockout mice, leading to restored formation of hemidesmosomes. These mice will be a valuable tool for studies of organs deficient in laminin-332 and the role of laminin-332 in skin, including wound healing.

View details for DOI 10.1371/journal.pone.0045546

View details for PubMedID 23029085