{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:41:36Z","timestamp":1793126496791,"version":"4.5.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019725","name":"DEBRA Austria","doi-asserted-by":"publisher","award":["Roopenian 2"],"award-info":[{"award-number":["Roopenian 2"]}],"id":[{"id":"10.13039\/501100019725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011960","name":"Debra International","doi-asserted-by":"publisher","award":["Roopenian 1"],"award-info":[{"award-number":["Roopenian 1"]}],"id":[{"id":"10.13039\/501100011960","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005946","name":"Jackson Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The <jats:italic>Lamc2<jats:sup>jeb<\/jats:sup><\/jats:italic> junctional epidermolysis bullosa (EB) mouse model has been used to demonstrate that significant genetic modification of EB symptoms is possible, identifying as modifiers <jats:italic>Col17a1<\/jats:italic> and six other quantitative trait loci, several with strong candidate genes including dystonin (<jats:italic>Dst\/Bpag1<\/jats:italic>). Here, CRISPR\/Cas9 was used to alter exon 23 in mouse skin specific isoform <jats:italic>Dst-e<\/jats:italic> (Ensembl GRCm38 transcript name Dst-213, transcript ID ENSMUST00000183302.5, protein size 2639AA) and validate a proposed arginine\/glutamine difference at amino acid p1226 in B6 versus 129 mice as a modifier of EB. Frame shift deletions (FSD) in mouse <jats:italic>Dst-e<\/jats:italic> exon 23 (<jats:italic>Dst-e<jats:sup>FSD\/FSD<\/jats:sup><\/jats:italic>) were also identified that cause mice carrying wild-type <jats:italic>Lamc2<\/jats:italic> to develop a phenotype similar to human EB simplex without dystonia musculorum. When combined, <jats:italic>Dst-e<jats:sup>FSD\/FSD<\/jats:sup><\/jats:italic> modifies <jats:italic>Lamc2<jats:sup>jeb\/jeb<\/jats:sup><\/jats:italic> (FSD+<jats:italic>jeb<\/jats:italic>) induced disease in unexpected ways implicating an altered balance between DST-e (BPAG1e) and a rarely reported rodless DST-eS (BPAG1eS) in epithelium as a possible mechanism. Further, FSD+<jats:italic>jeb<\/jats:italic> mice with pinnae removed are found to provide a test bed for studying internal epithelium EB disease and treatment without severe skin disease as a limiting factor while also revealing and accelerating significant nasopharynx symptoms present but not previously noted in <jats:italic>Lamc2<jats:sup>jeb\/jeb<\/jats:sup><\/jats:italic> mice.<\/jats:p>","DOI":"10.1371\/journal.pone.0293218","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T17:48:01Z","timestamp":1698342481000},"page":"e0293218","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dystonin modifiers of junctional epidermolysis bullosa and models of epidermolysis bullosa simplex without dystonia musculorum"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-232X","authenticated-orcid":true,"given":"Thomas J.","family":"Sproule","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Y.","family":"Wilpan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7678-3062","authenticated-orcid":true,"given":"John J.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0350-4602","authenticated-orcid":true,"given":"Benjamin E.","family":"Low","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudai","family":"Kabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Ushiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riichiro","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3620-8386","authenticated-orcid":true,"given":"Michael V.","family":"Wiles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derry C.","family":"Roopenian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-5430","authenticated-orcid":true,"given":"John P.","family":"Sundberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"issue":"4","key":"pone.0293218.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":"The British journal of dermatology"},{"issue":"1","key":"pone.0293218.ref002","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12876-018-0771-5","article-title":"A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa\u2014case report and literature review.","volume":"18","author":"A Michalak","year":"2018","journal-title":"BMC Gastroenterol."},{"issue":"2","key":"pone.0293218.ref003","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2302\/kjm.2014-0013-RE","article-title":"Advances in Gene\/Cell Therapy in Epidermolysis Bullosa.","volume":"64","author":"EM Murauer","year":"2015","journal-title":"Keio J Med"},{"issue":"8","key":"pone.0293218.ref004","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmg.2005.039685","article-title":"Epidermolysis bullosa. 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