{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:59:07Z","timestamp":1791118747368,"version":"4.1.0"},"reference-count":70,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,6,2]]},"abstract":"<jats:p>In patients with pemphigus vulgaris (PV), autoantibodies against desmoglein 3 (Dsg3) cause loss of cell\u2013cell adhesion of keratinocytes in the basal and immediate suprabasal layers of stratified squamous epithelia. The pathology, at least partially, may depend on protease release from keratinocytes, but might also result from antibodies interfering with an adhesion function of Dsg3. However, a direct role of desmogleins in cell adhesion has not been shown. To test whether Dsg3 mediates adhesion, we genetically engineered mice with a targeted disruption of the DSG3 gene. DSG3 \u2212\/\u2212 mice had no DSG3 mRNA by RNase protection assay and no Dsg3 protein by immunofluorescence (IF) and immunoblots. These mice were normal at birth, but by 8\u201310 d weighed less than DSG3 +\/\u2212 or +\/+ littermates, and at around day 18 were grossly runted. We speculated that oral lesions (typical in PV patients) might be inhibiting food intake, causing this runting. Indeed, oropharyngeal biopsies showed erosions with histology typical of PV, including suprabasilar acantholysis and \u201ctombstoning\u201d of basal cells. EM showed separation of desmosomes. Traumatized skin also had crusting and suprabasilar acantholysis. Runted mice showed hair loss at weaning. The runting and hair loss phenotype of DSG3 \u2212\/\u2212 mice is identical to that of a previously reported mouse mutant, balding (bal). Breeding indicated that bal is coallelic with the targeted mutation. We also showed that bal mice lack Dsg3 by IF, have typical PV oral lesions, and have a DSG3 gene mutation. These results demonstrate the critical importance of Dsg3 for adhesion in deep stratified squamous epithelia and suggest that pemphigus autoantibodies might interfere directly with such a function.<\/jats:p>","DOI":"10.1083\/jcb.137.5.1091","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:47:50Z","timestamp":1027702070000},"page":"1091-1102","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":361,"title":["Targeted Disruption of the Pemphigus Vulgaris Antigen (Desmoglein 3) Gene in Mice Causes Loss of Keratinocyte Cell Adhesion with a Phenotype Similar to Pemphigus Vulgaris"],"prefix":"10.1083","volume":"137","author":[{"given":"Peter J.","family":"Koch","sequence":"first","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M G.","family":"Mahoney","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Pulkkinen","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jouni","family":"Uitto","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Shultz","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George F.","family":"Murphy","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Whitaker-Menezes","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Stanley","sequence":"additional","affiliation":[{"name":"*Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; \u2021Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107; and \u00a7The Jackson Laboratory, Bar Harbor, Maine 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