{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:16:35Z","timestamp":1792034195330,"version":"4.4.0"},"reference-count":77,"publisher":"The Company of Biologists","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,3,1]]},"abstract":"<jats:p>The \u03b16\u03b24 integrin is located at the basal surface of keratinocytes, in hemidesmosomal structures that mediate stable adhesion of epidermal cells to the underlying basement membrane component laminin-5. The absence of \u03b16\u03b24 integrin causes junctional epidermolysis bullosa, a severe blistering disease of the skin leading to perinatal death, confirming its essential role in mediating strong keratinocyte adhesion. Several studies have suggested that \u03b16\u03b24 integrin can also regulate signaling cascades that control cell proliferation, survival and migration through a mechanism independent of its adhesive function. We have generated a conditional knockout mouse strain, in which the gene encoding the \u03b24 integrin subunit (Itgb4) was inactivated only in small stretches of the skin. These mice were viable and permitted an accurate analysis of the consequences of the loss of \u03b24 on various biological processes by comparing \u03b24-positive and -negative parts of the skin in the same animal. Despite the complete loss of hemidesmosomes in regions lacking \u03b16\u03b24 integrin, the distribution of a range of adhesion receptors and basement membrane proteins was unaltered. Moreover, loss of \u03b16\u03b24 did not affect squamous differentiation, proliferation or survival, except for areas in which keratinocytes had detached from the basement membrane. These in vivo observations were confirmed in vitro by using immortalized keratinocytes \u2013 derived from \u03b24-subunit conditional knockout mice \u2013 from which the gene encoding \u03b24 had been deleted by Cre-mediated recombination. Consistent with the established role of \u03b16\u03b24 in adhesion strengthening, its loss from cells was found to increase their motility. Our findings clearly demonstrate that, after birth, epidermal differentiation, proliferation and survival all proceed normally in the absence of \u03b16\u03b24, provided that cell adhesion is not compromised.<\/jats:p>","DOI":"10.1242\/jcs.01689","type":"journal-article","created":{"date-parts":[[2005,2,24]],"date-time":"2005-02-24T02:18:06Z","timestamp":1109211486000},"page":"1045-1060","source":"Crossref","is-referenced-by-count":80,"title":["Keratinocytes display normal proliferation, survival and differentiation in conditional \u03b24-integrin knockout mice"],"prefix":"10.1242","volume":"118","author":[{"given":"Karine","family":"Raymond","sequence":"first","affiliation":[{"name":"Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"Kreft","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Janssen","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jero","family":"Calafat","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnoud","family":"Sonnenberg","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042519195426900_REF1","doi-asserted-by":"crossref","unstructured":"Adams, J. 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