{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:27:23Z","timestamp":1778884043738,"version":"3.51.4"},"reference-count":44,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,4,20]]},"abstract":"<jats:p>Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering disease with both lethal and nonlethal forms, with most patients shown to have defects in laminin-5. We analyzed the location of mutations, gene expression levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB patients to determine how the type of genetic lesion influences the pathophysiology of JEB. Mutations within laminin-5 genes were diversely located, with the most severe forms of JEB correlating best with premature termination codons, rather than mapping to any particular protein domain. In all six JEB patients, the laminin-5 assembly intermediates we observed were as predicted by our previous work indicating that the \u03b13\u03b23\u03b32 heterotrimer assembles intracellularly via a \u03b23\u03b32 heterodimer intermediate. Since assembly precedes secretion, mutations that disrupt protein\u2013protein interactions needed for assembly are predicted to limit the secretion of laminin-5, and likely to interfere with function. However, our data indicate that typically the most severe mutations diminish mRNA stability, and serve as functional null alleles that block chain assembly by resulting in either a deficiency (in the nonlethal mitis variety) or a complete absence (in lethal Herlitz-JEB) of one of the chains needed for laminin-5 heterotrimer assembly.<\/jats:p>","DOI":"10.1084\/jem.187.8.1273","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1273-1283","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Extent of Laminin-5 Assembly and Secretion Effect Junctional Epidermolysis Bullosa Phenotype"],"prefix":"10.1084","volume":"187","author":[{"given":"Chihiro","family":"Matsui","sequence":"first","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phyllis","family":"Pereira","sequence":"additional","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Kathy","family":"Wang","sequence":"additional","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte F.","family":"Nelson","sequence":"additional","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Kutzkey","sequence":"additional","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Lanigan","sequence":"additional","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Woodley","sequence":"additional","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Morohashi","sequence":"additional","affiliation":[{"name":"From the *Department of Dermatology, Stanford University School of Medicine, Stanford, California, 94305; \u2021Department of Dermatology, Northwestern University Medical School, Chicago, Illinois, 60611; and \u00a7Department of Dermatology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-01 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