{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T03:10:57Z","timestamp":1770347457241,"version":"3.49.0"},"reference-count":61,"publisher":"The Company of Biologists","issue":"22","license":[{"start":{"date-parts":[[1999,11,15]],"date-time":"1999-11-15T00:00:00Z","timestamp":942624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Integrin \u03b24 null mice exhibit extensive epidermal detachment, reminiscent of the human skin blistering disease junctional epidermolysis bullosa associated with pyloric atresia. Hemidesmosomes, the stable adhesion structures of squamous epithelia, are not formed in the absence of \u03b16\u03b24. Null mutant mice die shortly after birth, but apart from their striking epithelial phenotype, no obvious developmental defects have been observed. To elucidate the cause of death in these mice, we generated transgenic mice with a heterologous construct consisting of the squamous epithelial-specific keratin-5 promoter and a human integrin \u03b24 subunit cDNA. The transgene was not expressed in the presence of endogenous \u03b24, probably as a result of competition for a limited pool of \u03b16 subunits. In a \u03b24 null background, however, the transgene was expressed, and its expression pattern followed that of squamous epithelial-specific keratins. These rescued pups appeared healthy and ultrastructural analysis revealed that the interspecies heterodimer \u03b16mouse\/\u03b24human was sufficient to trigger the assembly of hemidesmosomes. After a variable period of up to 48 hours after birth these animals began to exhibit haemorrhages at the plantar and palmar areas. We observed the formation of small blisters and found that the transgene was not detectably expressed in this region, which is devoid of hair follicles. The rescued neonates became increasingly cyanotic and died soon after the onset of this phenomenon. We performed a developmental study of the expression of \u03b24 in the complete respiratory tract, but we found no correlation between the spatiotemporal distribution of \u03b24 and the onset of the respiratory insufficiency. It became clear, however, that there was a gradual detachment of squamous epithelia in the oral and nasal cavities which led to obstruction of the respiratory tract, suggesting that in \u03b24 null and rescued mice, neonatal death was a direct consequence of decreased adhesion properties of hairless squamous epithelia, rather than a developmental defect of the lungs.<\/jats:p>","DOI":"10.1242\/jcs.112.22.3911","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T17:27:38Z","timestamp":1619371658000},"page":"3911-3922","source":"Crossref","is-referenced-by-count":11,"title":["Partial rescue of epithelial phenotype in integrin \u03b24 null mice by a keratin-5 promoter driven human integrin \u03b24 transgene"],"prefix":"10.1242","volume":"112","author":[{"given":"Ronald van der","family":"Neut","sequence":"first","affiliation":[{"name":"1 Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Sofia","family":"Cacha\u00e7o","sequence":"additional","affiliation":[{"name":"University of Lisbon, and Centre for Environmental Biology, University of Lisbon 2 Department of Zoology, Faculty of Sciences , , 1749-016 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f3lveig","family":"Thorsteinsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"University of Lisbon, and Centre for Environmental Biology, University of Lisbon 2 Department of Zoology, Faculty of Sciences , , 1749-016 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Janssen","sequence":"additional","affiliation":[{"name":"1 Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan","family":"Prins","sequence":"additional","affiliation":[{"name":"1 Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurjen","family":"Bulthuis","sequence":"additional","affiliation":[{"name":"3 Division of Molecular Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin van der","family":"Valk","sequence":"additional","affiliation":[{"name":"3 Division of Molecular Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jero","family":"Calafat","sequence":"additional","affiliation":[{"name":"1 Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnoud","family":"Sonnenberg","sequence":"additional","affiliation":[{"name":"1 Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1999,11,15]]},"reference":[{"key":"2024041523314517900_JOCES_112_22_3911C1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3109\/15419069409004431","article-title":"Developmental expression of nicein adhesion protein (laminin-5) subunits suggests multiple morphogenic roles","volume":"2","author":"Aberdam","year":"1994","journal-title":"Cell Adhes. 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