{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:28:49Z","timestamp":1787239729311,"version":"build-2736575974"},"reference-count":27,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"DEBRA Australia"},{"DOI":"10.13039\/100011167","name":"Australasian College of Dermatologists","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011167","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014607","name":"Royal Children's Hospital Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014607","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001036","name":"Australian Rotary Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001036","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australian Phenomics Network"},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Heterozygous missense mutations in the human COL7A1 gene \u2013 coding for collagen VII \u2013 lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR-Cas9 to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10\u2005weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of epidermolysis bullosa, which frequently show early lethality and severe disease, these mouse models, which to our knowledge are the first for DDEB, show no reduction in growth and survival, and \u2013 together with a relatively mild phenotype \u2013 represent a practically and ethically tractable tool for better understanding and treating epidermolysis bullosa.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.048082","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T08:05:11Z","timestamp":1619769911000},"source":"Crossref","is-referenced-by-count":9,"title":["Mouse models for dominant dystrophic epidermolysis bullosa carrying common human point mutations recapitulate the human disease"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6992-264X","authenticated-orcid":false,"given":"Blake R. C.","family":"Smith","sequence":"first","affiliation":[{"name":"Murdoch Children's Research Institute, Parkville, VIC 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-9840","authenticated-orcid":false,"given":"Cameron J.","family":"Nowell","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-4962","authenticated-orcid":false,"given":"Ingrid","family":"Hausser","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Heidelberg, Heidelberg 69120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gretzmeier","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4790-9943","authenticated-orcid":false,"given":"Susan J.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute, Parkville, VIC 3052, Australia"},{"name":"Dermatology Department, Faculty of Medicine, Dentistry and Health Sciences, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC 3050, Australia"},{"name":"Royal Children's Hospital, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Varigos","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"Dermatology Department, Faculty of Medicine, Dentistry and Health Sciences, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-507X","authenticated-orcid":false,"given":"Cristina","family":"Has","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-8048","authenticated-orcid":false,"given":"Johannes S.","family":"Kern","sequence":"additional","affiliation":[{"name":"Dermatology Department, Faculty of Medicine, Dentistry and Health Sciences, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-775X","authenticated-orcid":false,"given":"Ken C.","family":"Pang","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute, Parkville, VIC 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"Royal Children's Hospital, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"2021060411130822500_DMM048082C28","first-page":"459","volume-title":"Diagnostic Ultrastructure of Non-Neoplastic Diseases","author":"Anton-Lamprecht","year":"1992"},{"key":"2021060411130822500_DMM048082C1","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1038\/mt.2016.92","article-title":"Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy","volume":"24","author":"Bornert","year":"2016","journal-title":"Mol. 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