{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:58:29Z","timestamp":1791899909406,"version":"4.3.4"},"reference-count":63,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,6,14]]},"abstract":"<jats:p>Laminin 5 regulates anchorage and motility of epithelial cells through integrins \u03b16\u03b24 and \u03b13\u03b21, respectively. We used targeted disruption of the LAMA3 gene, which encodes the \u03b13 subunit of laminin 5 and other isoforms, to examine developmental functions that are regulated by adhesion to the basement membrane (BM). In homozygous null animals, profound epithelial abnormalities were detected that resulted in neonatal lethality, consistent with removal of all \u03b13-laminin isoforms from epithelial BMs. Alterations in three different cellular functions were identified. First, using a novel tissue adhesion assay, we found that the mutant BM could not induce stable adhesion by integrin \u03b16\u03b24, consistent with the presence of junctional blisters and abnormal hemidesmosomes. In the absence of laminin 5 function, we were able to detect a new ligand for integrin \u03b13\u03b21 in the epidermal BM, suggesting that basal keratinocytes can utilize integrin \u03b13\u03b21 to interact with an alternative ligand. Second, we identified a survival defect in mutant epithelial cells that could be rescued by exogenous laminin 5, collagen, or an antibody against integrin \u03b16\u03b24, suggesting that signaling through \u03b21 or \u03b24 integrins is sufficient for survival. Third, we detected abnormalities in ameloblast differentiation in developing mutant incisors indicating that events downstream of adhesion are affected in mutant animals. These results indicate that laminin 5 has an important role in regulating tissue organization, gene expression, and survival of epithelium.<\/jats:p>","DOI":"10.1083\/jcb.145.6.1309","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:45:41Z","timestamp":1027687541000},"page":"1309-1324","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":280,"title":["Targeted Disruption of the\n                    <i>LAMA3<\/i>\n                    Gene in Mice Reveals Abnormalities in Survival and Late Stage Differentiation of Epithelial Cells"],"prefix":"10.1083","volume":"145","author":[{"given":"Maureen C.","family":"Ryan","sequence":"first","affiliation":[{"name":"*Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; \u2021Department of Medicine, Division of Dermatology, University of Washington, Seattle, Washington 98198; \u2016Department of Pathobiology, University of Washington, Seattle, Washington 98198; and \u00a7Hormone Research Center, Chonnam National University, Kwangju 500-757, South Korea"},{"name":"*Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; \u2021Department of Medicine, Division of Dermatology, University of Washington, Seattle, Washington 98198; \u2016Department of Pathobiology, University of Washington, Seattle, Washington 98198; and \u00a7Hormone Research Center, Chonnam National University, Kwangju 500-757, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keesook","family":"Lee","sequence":"additional","affiliation":[{"name":"*Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; \u2021Department of Medicine, Division of Dermatology, University of Washington, Seattle, Washington 98198; \u2016Department of Pathobiology, University of Washington, Seattle, Washington 98198; and \u00a7Hormone Research Center, Chonnam National University, Kwangju 500-757, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Miyashita","sequence":"additional","affiliation":[{"name":"*Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; \u2021Department of Medicine, Division of Dermatology, University of Washington, Seattle, Washington 98198; \u2016Department of Pathobiology, University of Washington, Seattle, Washington 98198; and \u00a7Hormone Research Center, Chonnam National University, Kwangju 500-757, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Carter","sequence":"additional","affiliation":[{"name":"*Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; \u2021Department of Medicine, Division of Dermatology, University of Washington, Seattle, Washington 98198; \u2016Department of Pathobiology, University of Washington, Seattle, Washington 98198; and \u00a7Hormone Research Center, Chonnam National University, Kwangju 500-757, South Korea"},{"name":"*Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; \u2021Department of Medicine, Division of Dermatology, University of Washington, Seattle, Washington 98198; \u2016Department of Pathobiology, University of Washington, Seattle, Washington 98198; and \u00a7Hormone Research Center, Chonnam National University, Kwangju 500-757, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,6,14]]},"reference":[{"key":"2023072901250050500_B1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ng0394-299","article-title":"Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein\/kalinin (LAMININ-5)","volume":"6","author":"Aberdam","year":"1994","journal-title":"Nat Genet"},{"key":"2023072901250050500_B2","first-page":"255","article-title":"Developing teeth in epidermolysis bullosa hereditaria letalis. 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