Abstract
Cell-extracellular matrix interactions have important roles in many biological processes, including embryonic development, growth control and differentiation. Integrins are the principal receptors for extracellular matrix1. They are composed of non-covalently associated α and β chains1. Integrin oc6 can associate with either β1 or β4 (refs 2,3). Both integrin complexes are receptors for laminins, major components of basement membranes2,3. The distribution of α6 (refs 4–10) as well as studies using function-blocking antibodies have suggested an essential role for this laminin receptor during embryogenesis, in processes such as endoderm migration4,5 or kidney tubule formation9. Here we report that, surprisingly, mice lacking the α6 integrin chain develop to birth. However, they die at birth with severe blistering of the skin and other epithelia, a phenotype reminiscent of the human disorder epidermolysis bullosa11. Hemidesmo-somes are absent in mutant tissue. This absence is likely to result from the lack of α6/β4, the only integrin in hemidesmosomes of stratified squamous and transitional epithelia12–14. Mutations in the genes encoding integrin β4 and chains of laminin-5 have been implicated in junctional epidermolysis bullosa15–18. Our study provides evidence that some forms of epidermolysis bullosa may originate from defects of the α6 gene.
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Georges-Labouesse, E., Messaddeq, N., Yehia, G. et al. Absence of integrin α6 leads to epidermolysis bullosa and neonatal death in mice. Nat Genet 13, 370–373 (1996). https://doi.org/10.1038/ng0796-370
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DOI: https://doi.org/10.1038/ng0796-370
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