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Epithelial detachment due to absence of hemidesmosomes in integrin β4 null mice

Nature Genetics volume 13, pages 366–369 (1996)Cite this article

Abstract

Integrins are heterodimeric transmembrane glyco-proteins which are engaged in a variety of cellular functions, such as adhesion, migration and differentiation1. The integrin α6β4 is expressed on squa-mous epithelia2, on subsets of endothelial cells3, immature thymocytes4 and on Schwann cells and fibroblasts in the peripheral nervous system5. In stratified epithelia, α6β4 is concentrated in specialised adhesion structures, called hemidesmosomes6,7, which are implicated in the stable attachment of the basal cells to the underlying basement membrane by connecting the intermediate filaments with the extracellular matrix8. The nature of the interactions between the various hemidesmosomal proteins, that lead to the formation of hemidesmosomes is poorly understood. To study the contribution of the integrin α6β4 in hemidesmosome formation and their anchoring properties, we inactivated the β4 gene in mice by targeted gene disruption. Homozygous β4 null mice died shortly after birth and displayed extensive detachment of the epidermis and other squamous epithelia. The dramatically reduced adhesive properties of the skin was accompanied by the absence of hemidesmosomes at the basal surface of keratinocytes. No evidence was found for impaired T-cell development, nor for defects in myelination in the peripheral nervous system.

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Authors and Affiliations

  1. Divisions of Cell Biology of the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Ronald van der Neut, Jero Calafat, Carien M. Niessen & Arnoud Sonnenberg

  2. Divisions of Molecular Genetics of the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Paul Krimpenfort

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van der Neut, R., Krimpenfort, P., Calafat, J. et al. Epithelial detachment due to absence of hemidesmosomes in integrin β4 null mice. Nat Genet 13, 366–369 (1996). https://doi.org/10.1038/ng0796-366

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