| First Author | Dowling J | Year | 1996 |
| Journal | J Cell Biol | Volume | 134 |
| Issue | 2 | Pages | 559-72 |
| PubMed ID | 8707838 | Mgi Jnum | J:77644 |
| Mgi Id | MGI:2182206 | Doi | 10.1083/jcb.134.2.559 |
| Citation | Dowling J, et al. (1996) Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival. J Cell Biol 134(2):559-72 |
| abstractText | The integrin heterodimer alpha 6 beta 4 is expressed in many epithelia and in Schwann cells. In stratified epithelia, alpha 6 beta 4 couple with BPAG1-e and BPAG2 to form hemidesmosomes, attaching externally to laminin and internally to the keratin cytoskeleton. To explore the function of this atypical integrin, and its relation to conventional actin-associated integrins, we targeted the removal of the beta 4 gene in mice. Tissues that express alpha 6 beta 4 are grossly affected. Stratified tissues are devoid of hemidesmosomes, display only a very fragile attachment to the basal lamina, and exhibit signs of degeneration and tissue disorganization. Simple epithelia which express alpha 6 beta 4 are also defective in adherence, even though they do not form hemidesmosomes. In the absence of beta 4, alpha 6 is dramatically downregulated, and other integrins do not appear to compensate for the loss of this heterodimer. These data have important implications for understanding integrin function in cell-substratum adhesion, cell survival and differentiation, and for understanding the role of alpha 6 beta 4 in junctional epidermolysis bullosa, an often lethal human disorder with pathology similar to our mice. |
