{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T21:27:25Z","timestamp":1776288445067,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,8,26]],"date-time":"2013-08-26T00:00:00Z","timestamp":1377475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"name":"DFG","award":["SFB492A17"],"award-info":[{"award-number":["SFB492A17"]}]},{"name":"DFG","award":["Pa689\/10-1"],"award-info":[{"award-number":["Pa689\/10-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To generate doxycycline\u2010inducible human tumor necrosis factor \u03b1 (TNF\u03b1)\u2013transgenic mice to overcome a major disadvantage of existing transgenic mice with constitutive expression of TNF\u03b1, which is the limitation in crossing them with various knockout or transgenic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A transgenic mouse line that expresses the human TNF\u03b1 cytokine exclusively after doxycycline administration was generated and analyzed for the onset of diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Doxycycline\u2010inducible human TNF\u03b1\u2013transgenic mice developed an inflammatory arthritis\u2013 and psoriasis\u2010like phenotype, with fore and hind paws being prominently affected. The formation of \u201csausage digits\u201d with characteristic involvement of the distal interphalangeal joints and nail malformation was observed. Synovial hyperplasia, enthesitis, cartilage and bone alterations, formation of pannus tissue, and inflammation of the skin epidermis and nail matrix appeared as early as 1 week after the treatment of mice with doxycycline and became aggravated over time. The abrogation of human TNF\u03b1 expression by the removal of doxycycline 6 weeks after beginning stimulation resulted in fast resolution of the most advanced macroscopic and histologic disorders, and 3\u20136 weeks later, only minimal signs of disease were visible.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Upon doxycycline administration, the doxycycline\u2010inducible human TNF\u03b1\u2013transgenic mouse displays the major features of inflammatory arthritis. It represents a unique animal model for studying the molecular mechanisms of arthritis, especially the early phases of disease genesis and tissue remodeling steps upon abrogation of TNF\u03b1 expression. Furthermore, unlimited crossing of doxycycline\u2010inducible human TNF\u03b1\u2013transgenic mice with various knockout or transgenic mice opens new possibilities for unraveling the role of various signaling molecules acting in concert with TNF\u03b1.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38026","type":"journal-article","created":{"date-parts":[[2013,6,5]],"date-time":"2013-06-05T16:11:57Z","timestamp":1370448717000},"page":"2290-2300","source":"Crossref","is-referenced-by-count":24,"title":["Doxycycline\u2010Induced Expression of Transgenic Human Tumor Necrosis Factor \u03b1 in Adult Mice Results in Psoriasis\u2010like Arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"Eugen","family":"Retser","sequence":"first","affiliation":[{"name":"ZMBE and University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Schied","sequence":"additional","affiliation":[{"name":"ZMBE and University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris V.","family":"Skryabin","sequence":"additional","affiliation":[{"name":"ZMBE, IZKF, and University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[{"name":"University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janos M.","family":"Kanczler","sequence":"additional","affiliation":[{"name":"University of Southampton Medical School Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Hamann","sequence":"additional","affiliation":[{"name":"German Sport University Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Niehoff","sequence":"additional","affiliation":[{"name":"German Sport University Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Hermann","sequence":"additional","affiliation":[{"name":"University of Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Eisenbl\u00e4tter","sequence":"additional","affiliation":[{"name":"University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Wachsmuth","sequence":"additional","affiliation":[{"name":"University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Pap","sequence":"additional","affiliation":[{"name":"University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter L. E. M.","family":"van Lent","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Loser","sequence":"additional","affiliation":[{"name":"University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Roth","sequence":"additional","affiliation":[{"name":"University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Zaucke","sequence":"additional","affiliation":[{"name":"University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ludwig","sequence":"additional","affiliation":[{"name":"ZMBE and University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktor","family":"Wixler","sequence":"additional","affiliation":[{"name":"ZMBE and University Hospital Muenster Muenster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00237-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2287"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.01.007"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-003-0125-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.01.017"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.077800"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30418"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34315"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2917"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04978.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.148551"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6793-7-13"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200386"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1638"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-7-108"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1008647"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2009.88"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070906"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05663"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507804200"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.02.007"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930701694667"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0006"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38026","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.38026","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:33:16Z","timestamp":1696602796000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.38026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,26]]},"references-count":23,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1002\/art.38026"],"URL":"https:\/\/doi.org\/10.1002\/art.38026","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,26]]}}}