{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:42:48Z","timestamp":1759333368966,"version":"3.37.3"},"reference-count":15,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR063070"],"award-info":[{"award-number":["R01 AR063070"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the <jats:italic>Col7a1<\/jats:italic> gene. The <jats:italic>Col7a1<\/jats:italic> gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the <jats:italic>Col7a1<\/jats:italic> gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils. This presents clinically as chronic blistering, scarring, and fibrosis, often leading to the development of cutaneous squamous cell carcinoma. Patients also experience persistent pain and pruritus. Pain management and supportive bandaging remain the primary treatment options. The pathology of recessive dystrophic epidermolysis bullosa was first described in the 1980s, and there has since been a multitude of encouraging treatment options developed. However, <jats:italic>in vivo<\/jats:italic> research has been hindered by inadequate models of the disease. The various mouse models in existence possess longevity and surface area constraints, or do not adequately model a normal human disease state. In this paper, we describe a novel rat model of recessive dystrophic epidermolysis bullosa that offers an alternative to previous murine models. An 8-base pair deletion was induced in the <jats:italic>Col7a1<\/jats:italic> gene of Lewis rats, which was subsequently found to cause a premature stop codon downstream. Homozygous mutants presented with a fragile and chronically blistered phenotype postnatally. Further histological analysis revealed subepidermal clefting and the absence of anchoring fibrils. The generation of this novel model offers researchers an easily maintained organism that possesses a larger surface area for experimental topical and transfused therapies to be tested, which may provide great utility in the future study of this debilitating disease.<\/jats:p>","DOI":"10.1371\/journal.pone.0302991","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:24:22Z","timestamp":1715275462000},"page":"e0302991","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype"],"prefix":"10.1371","volume":"19","author":[{"given":"William","family":"Stone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5707-9416","authenticated-orcid":true,"given":"Chloe","family":"Strege","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4347-2505","authenticated-orcid":true,"given":"Aron M.","family":"Geurts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Grzybowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9557-217X","authenticated-orcid":true,"given":"Megan","family":"Riddle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Lees","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-2550","authenticated-orcid":true,"given":"Cindy","family":"Eide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas R.","family":"Keene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara F.","family":"Tufa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davis","family":"Seelig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-9964","authenticated-orcid":true,"given":"John","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0957-4380","authenticated-orcid":true,"given":"Jakub","family":"Tolar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"issue":"4","key":"pone.0302991.ref001","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/bjd.18921","article-title":"Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility","volume":"183","author":"C Has","year":"2020","journal-title":"Br J Dermatol"},{"issue":"1","key":"pone.0302991.ref002","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41572-020-0210-0","article-title":"Epidermolysis bullosa","volume":"6","author":"A Bardhan","year":"2020","journal-title":"Nat Rev Dis Primers"},{"issue":"3","key":"pone.0302991.ref003","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jdermsci.2021.11.004","article-title":"Current topics in Epidermolysis bullosa: Pathophysiology and therapeutic challenges","volume":"104","author":"K Natsuga","year":"2021","journal-title":"J Dermatol Sci"},{"key":"pone.0302991.ref004","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2147\/TCRM.S386923","article-title":"Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects","volume":"19","author":"PC Hou","year":"2023","journal-title":"Ther Clin Risk Manag"},{"issue":"1","key":"pone.0302991.ref005","doi-asserted-by":"crossref","first-page":"3\u201313","DOI":"10.1111\/vde.12176","article-title":"Epidermolysis bullosa in animals: a review","volume":"26","author":"GX Medeiros","year":"2015","journal-title":"Vet Dermatol"},{"issue":"4","key":"pone.0302991.ref006","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.jid.2021.09.008","article-title":"Systemic Collagen VII Replacement Therapy for Advanced Recessive Dystrophic Epidermolysis Bullosa","volume":"142","author":"C Gretzmeier","year":"2022","journal-title":"J Invest Dermatol"},{"issue":"Pt 21","key":"pone.0302991.ref007","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1242\/jcs.112.21.3641","article-title":"Targeted inactivation of the type VII collagen gene (Col7a1) in mice results in severe blistering phenotype: a model for recessive dystrophic epidermolysis bullosa","volume":"112","author":"S Heinonen","year":"1999","journal-title":"J Cell Sci"},{"issue":"10","key":"pone.0302991.ref008","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/labinvest.2017.85","article-title":"Rapid generation of Col7a1(-\/-) mouse model of recessive dystrophic epidermolysis bullosa and partial rescue via immunosuppressive dermal mesenchymal stem cells","volume":"97","author":"BR Webber","year":"2017","journal-title":"Lab Invest"},{"issue":"5","key":"pone.0302991.ref009","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1172\/JCI34292","article-title":"A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy","volume":"118","author":"A Fritsch","year":"2008","journal-title":"J Clin Invest"},{"issue":"5","key":"pone.0302991.ref010","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1021\/acschemneuro.6b00415","article-title":"Comeback of the Rat in Biomedical Research","volume":"8","author":"JR Homberg","year":"2017","journal-title":"ACS Chem Neurosci"},{"issue":"12","key":"pone.0302991.ref011","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1111\/exd.14411","article-title":"Immunological mechanisms underlying progression of chronic wounds in recessive dystrophic epidermolysis bullosa","volume":"30","author":"L Huitema","year":"2021","journal-title":"Exp Dermatol"},{"issue":"3","key":"pone.0302991.ref012","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00441-015-2216-6","article-title":"Molecular architecture and function of the hemidesmosome","volume":"360","author":"G Walko","year":"2015","journal-title":"Cell Tissue Res"},{"key":"pone.0302991.ref013","volume-title":"Skin Aging Handbook: An integrated approach to biochemistry and product development","author":"GK Menon","year":"2008","edition":"1"},{"issue":"1","key":"pone.0302991.ref014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jat.3004","article-title":"Animal models for percutaneous absorption","volume":"35","author":"EC Jung","year":"2015","journal-title":"J Appl Toxicol"},{"issue":"6061","key":"pone.0302991.ref015","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.1210789","article-title":"Empathy and pro-social behavior in rats","volume":"334","author":"I Ben-Ami Bartal","year":"2011","journal-title":"Science"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0302991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:24:31Z","timestamp":1715275471000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0302991"}},"subtitle":[],"editor":[{"given":"Michael","family":"Klymkowsky","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":15,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0302991","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2024,5,9]]}}}