{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:06:14Z","timestamp":1790744774315,"version":"4.1.0"},"reference-count":51,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[1995,11,1]],"date-time":"1995-11-01T00:00:00Z","timestamp":815184000000},"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":[[1995,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Point mutations in the keratin intermediate filament genes for keratin 5 or keratin 14 are known to cause hereditary skin blistering disorders such as epidermolysis bullosa simplex, in which epidermal keratinocytes are extremely fragile and the skin blisters on mild trauma. We show that in 2 phenotypically diverse cases of epidermolysis bullosa simplex, the keratin mutations result in a thermoinstability of the intermediate filament cytoskeleton which can be reproducibly demonstrated even in the presence of tissue culture-induced keratins and in conditions where filament fragility is not otherwise obvious.<\/jats:p>\n               <jats:p>SV40-T antigen and HPV16 (E6\/E7) immortalised keratinocyte cell lines were examined, established from control and epidermolysis bullosa simplex-affected individuals with either severe (Dowling-Meara) or mild (Weber-Cockayne) forms of the disease. In standard tissue culture conditions no significant and consistent abnormality of the keratin cytoskeleton could be demonstrated. However after thermal stress a reduced stability of the keratin filaments was demonstrable in the epidermolysis bullosa simplex cell lines, with filaments breaking into aggregates similar to those seen in skin from EBS patients. These aggregates were maximal at 15 minutes after heat shock and the filament network structure was substantially reversed by 60 minutes.<\/jats:p>\n               <jats:p>Differences were also seen in the cells during respreading after replating: cells containing mutant keratins were slower to respread than controls and fine aggregates were seen at the cell margins in the Dowling-Meara derived cell line. Such delays in restoring the normal intermediate filament network after physiological processes involving cytoskeleton remodelling may render the cells vulnerable to cytolysis in vivo if physically challenged during this time window. The steady reduction in the mitotic index of the epidermis during the first few years of life could then explain the clinical improvement which is frequently observed in growing children.<\/jats:p>","DOI":"10.1242\/jcs.108.11.3463","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T02:30:32Z","timestamp":1619231432000},"page":"3463-3471","source":"Crossref","is-referenced-by-count":68,"title":["Temperature sensitivity of the keratin cytoskeleton and delayed spreading of keratinocyte lines derived from ebs patients"],"prefix":"10.1242","volume":"108","author":[{"given":"S. M.","family":"Morley","sequence":"first","affiliation":[{"name":"1 CRC Cell Structure Research Group, Cancer Research Campaign Laboratories, Department of Anatomy & Physiology, Medical Sciences Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. R.","family":"Dundas","sequence":"additional","affiliation":[{"name":"1 CRC Cell Structure Research Group, Cancer Research Campaign Laboratories, Department of Anatomy & Physiology, Medical Sciences Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L.","family":"James","sequence":"additional","affiliation":[{"name":"1 CRC Cell Structure Research Group, Cancer Research Campaign Laboratories, Department of Anatomy & Physiology, Medical Sciences Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Gupta","sequence":"additional","affiliation":[{"name":"1 CRC Cell Structure Research Group, Cancer Research Campaign Laboratories, Department of Anatomy & Physiology, Medical Sciences Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. A.","family":"Brown","sequence":"additional","affiliation":[{"name":"University of Dundee, Dundee DD1 4HN 2 Department of Mathematics , , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. J.","family":"Sexton","sequence":"additional","affiliation":[{"name":"3 Experimental Dermatology Laboratories, Medical College of the Royal London Hospital, London E1 6BL, UK"},{"name":"4 Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. A.","family":"Navsaria","sequence":"additional","affiliation":[{"name":"3 Experimental Dermatology Laboratories, Medical College of the Royal London Hospital, London E1 6BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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