{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:06:45Z","timestamp":1790744805036,"version":"4.1.0"},"reference-count":28,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,2,5]]},"abstract":"<jats:p>The Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM) is a severe blistering disease inherited in an autosomal-dominant fashion. Here we report the generation of a mouse model that allows focal activation of a mutant keratin 14 allele in epidermal stem cells upon topical administration of an inducer, resulting in EBS phenotypes in treated areas. Using laser capture microdissection, we show that induced blisters healed by migration of surrounding nonphenotypic stem cells into the wound bed. This observation provides an explanation for the lack of mosaic forms of EBS-DM. In addition, we show that decreased mutant keratin 14 expression resulted in normal morphology and functions of the skin. Our results have important implications for gene therapy of EBS and other dominantly inherited diseases.<\/jats:p>","DOI":"10.1083\/jcb.152.3.651","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:46:23Z","timestamp":1027701983000},"page":"651-656","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":118,"title":["An Inducible Mouse Model for Epidermolysis Bullosa Simplex"],"prefix":"10.1083","volume":"152","author":[{"given":"Tongyu","family":"Cao","sequence":"first","affiliation":[{"name":"aDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ann","family":"Longley","sequence":"additional","affiliation":[{"name":"aDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"aDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030"},{"name":"bDepartment of Dermatology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis R.","family":"Roop","sequence":"additional","affiliation":[{"name":"aDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030"},{"name":"bDepartment of Dermatology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,2,5]]},"reference":[{"key":"2023072211270038500_Alexeevetal2000","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/71901","article-title":"Localized in vivo genotypic and phenotypic correction of the albino mutation in skin by RNA-DNA oligonucleotide","volume":"18","author":"Alexeev","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"2023072211270038500_Anton-LamprechtandSchnyder1982","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000250096","article-title":"Epidermolysis bullosa herpetiformis Dowling-Meara. Report of a case and pathomorphogenesis","volume":"164","author":"Anton-Lamprecht","year":"1982","journal-title":"Dermatologica."},{"key":"2023072211270038500_Arinetal2001","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1083\/jcb.152.3.645","article-title":"Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders","volume":"152","author":"Arin","year":"2001","journal-title":"J. Cell Biol."},{"key":"2023072211270038500_Bertonetal2000","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<160::AID-GENE20>3.0.CO;2-#","article-title":"Characterization of an inducible, epidermal-specific knockout systemdifferential expression of lacZ in different Cre reporter mouse strains","volume":"26","author":"Berton","year":"2000","journal-title":"Genesis."},{"key":"2023072211270038500_Chanetal1994","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1101\/gad.8.21.2574","article-title":"A human keratin 14 \u201cknockout\u201dthe absence of K14 leads to severe epidermolysis bullosa simplex and a function for an intermediate filament protein","volume":"8","author":"Chan","year":"1994","journal-title":"Genes Dev."},{"key":"2023072211270038500_Chenetal1995","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/1523-1747.ep12323846","article-title":"Keratin 14 gene mutations in patients with epidermolysis bullosa simplex","volume":"105","author":"Chen","year":"1995","journal-title":"J. Invest. Dermatol."},{"key":"2023072211270038500_Cole-Straussetal1996","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1126\/science.273.5280.1386","article-title":"Correction of the mutation responsible for sickle cell anemia by an RNA-DNA oligonucleotide","volume":"273","author":"Cole-Strauss","year":"1996","journal-title":"Science."},{"key":"2023072211270038500_Coulombe1993","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0955-0674(05)80004-3","article-title":"The cellular and molecular biology of keratinsbeginning a new era","volume":"5","author":"Coulombe","year":"1993","journal-title":"Curr. Opin. Cell Biol."},{"key":"2023072211270038500_DowlingandMeara1954","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1365-2133.1954.tb12605.x","article-title":"Epidermolysis bullosa dermatitis herpetiformis","volume":"66","author":"Dowling","year":"1954","journal-title":"Br. J. Dermatol."},{"key":"2023072211270038500_HatzfeldandWeber1990","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1083\/jcb.110.4.1199","article-title":"The coiled coil of in vitro assembled keratin filaments is a heterodimer of type I and II keratinsuse of site-specific mutagenesis and recombinant protein expression","volume":"110","author":"Hatzfeld","year":"1990","journal-title":"J. Cell Biol."},{"key":"2023072211270038500_Jonkmanetal1996","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/1523-1747.ep12365805","article-title":"Effects of keratin 14 ablation on the clinical and cellular phenotype in a kindred with recessive epidermolysis bullosa simplex","volume":"107","author":"Jonkman","year":"1996","journal-title":"J. Invest. Dermatol."},{"key":"2023072211270038500_Kellendonketal1996","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1093\/nar\/24.8.1404","article-title":"Regulation of Cre recombinase activity by the synthetic steroid RU 486","volume":"24","author":"Kellendonk","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"2023072211270038500_Letaietal1993","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1073\/pnas.90.8.3197","article-title":"Disease severity correlates with position of keratin point mutations in patients with epidermolysis bullosa simplex","volume":"90","author":"Letai","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072211270038500_Lloydetal1995","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1083\/jcb.129.5.1329","article-title":"The basal keratin network of stratified squamous epitheliadefining K15 function in the absence of K14","volume":"129","author":"Lloyd","year":"1995","journal-title":"J. Cell Biol."},{"key":"2023072211270038500_Marinkovichetal1999","first-page":"690","article-title":"Hereditary epidermolysis bullosa","volume-title":"Fitzpatrick's dermatology in general medicine","author":"Marinkovich","year":"1999"},{"key":"2023072211270038500_McGrathetal1992","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1365-2133.1992.tb11813.x","article-title":"Epidermolysis bullosa simplex (Dowling-Meara). A clinicopathological review","volume":"126","author":"McGrath","year":"1992","journal-title":"Br. J. Dermatol."},{"key":"2023072211270038500_Molletal1982","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0092-8674(82)90400-7","article-title":"The catalog of human cytokeratinspatterns of expression in normal epithelia, tumors and cultured cells","volume":"31","author":"Moll","year":"1982","journal-title":"Cell."},{"key":"2023072211270038500_Morleyetal1995","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1242\/jcs.108.11.3463","article-title":"Temperature sensitivity of the keratin cytoskeleton and delayed spreading of keratinocyte lines derived from EBS patients","volume":"108","author":"Morley","year":"1995","journal-title":"J. Cell Sci."},{"key":"2023072211270038500_Palleretal1994","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJM199411243312103","article-title":"Genetic and clinical mosaicism in a type of epidermal nevus","volume":"331","author":"Paller","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"2023072211270038500_Pottenetal1987","first-page":"461","article-title":"Measurement of the transit time for cells through the epidermis and stratum corneum of the mouse and guinea-pig","volume":"20","author":"Potten","year":"1987","journal-title":"Cell Tissue Kinet."},{"key":"2023072211270038500_Quinlanetal1985","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1749-6632.1985.tb50418.x","article-title":"Patterns of expression and organization of cytokeratin intermediate filaments","volume":"455","author":"Quinlan","year":"1985","journal-title":"Ann. NY Acad. Sci."},{"key":"2023072211270038500_RothnagelandRoop1995","first-page":"211","article-title":"Analysis, diagnosis, and molecular genetics of keratin disorders","volume":"1995","author":"Rothnagel","year":"1995","journal-title":"Current Opininon in Dermatology"},{"key":"2023072211270038500_Ruggetal1994","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1101\/gad.8.21.2563","article-title":"A functional \u201cknockout\u201d of human keratin 14","volume":"8","author":"Rugg","year":"1994","journal-title":"Genes Dev."},{"key":"2023072211270038500_Steinert1990","doi-asserted-by":"crossref","first-page":"8766","DOI":"10.1016\/S0021-9258(19)38954-9","article-title":"The two-chain coiled-coil molecule of native epidermal keratin intermediate filaments is a type I-type II heterodimer","volume":"265","author":"Steinert","year":"1990","journal-title":"J. Biol. Chem."},{"key":"2023072211270038500_SteinertandRoop1988","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.bi.57.070188.003113","article-title":"Molecular and cellular biology of intermediate filaments","volume":"57","author":"Steinert","year":"1988","journal-title":"Annu. Rev. Biochem."},{"key":"2023072211270038500_Vassaretal1991","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0092-8674(91)90645-F","article-title":"Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease","volume":"64","author":"Vassar","year":"1991","journal-title":"Cell."},{"key":"2023072211270038500_Wangetal1995","first-page":"279","article-title":"TGF alpha and v-fos cooperation in transgenic mouse epidermis induces aberrant keratinocyte differentiation and stable, autonomous papillomas","volume":"10","author":"Wang","year":"1995","journal-title":"Oncogene."},{"key":"2023072211270038500_Wojciketal2000","doi-asserted-by":"crossref","first-page":"5248","DOI":"10.1128\/MCB.20.14.5248-5255.2000","article-title":"Delayed wound healing in keratin 6a knockout mice","volume":"20","author":"Wojcik","year":"2000","journal-title":"Mol. Cell Biol."}],"container-title":["The Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/152\/3\/651\/1509634\/0010103.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/152\/3\/651\/1509634\/0010103.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T11:27:50Z","timestamp":1690025270000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/152\/3\/651\/45770\/An-Inducible-Mouse-Model-for-Epidermolysis-Bullosa"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,2,5]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2001,2,5]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.152.3.651","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,2,5]]}}}