{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:10:48Z","timestamp":1791846648126,"version":"4.3.4"},"reference-count":19,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":1634,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"name":"Guangdong Provincial Science & Technology Project","award":["2013B060300025"],"award-info":[{"award-number":["2013B060300025"]}]},{"name":"Guangdong Provincial Science & Technology Project","award":["2013B040400007"],"award-info":[{"award-number":["2013B040400007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Tumor necrosis factor alpha (TNF\u03b1) plays a key role in the pathogenesis of rheumatoid arthritis (RA). Blockade of TNF\u03b1 by monoclonal antibody has been widely used for the therapy of RA since the 1990s; however, its mechanism of efficacy, and potential safety concerns of the treatment are still not fully understood. This study sought to establish a transgenic arthritic mouse model by overexpressing human TNF\u03b1 (hTNF\u03b1) and to apply this model as a means to evaluate therapeutic consequences of TNF\u03b1 inhibitors. The transgenic mouse line (TgTC) with FVB background was generated by incorporating 3\u2032-modified hTNF\u03b1 gene sequences. A progressively erosive polyarthritis developed in the TgTC mice, with many characteristics observed in human rheumatoid arthritis, including polyarticular swelling, impairment of movement, synovial hyperplasia, and cartilage and bone erosion. Gene expression analysis demonstrated that hTNF\u03b1 is not only expressed in hyperplastic synovial membrane, but also in tissues without lesions, including brain, lung and kidney. Treatment of the TgTC mice with anti-hTNF\u03b1 monoclonal antibodies (mAb) significantly decreased the level of hTNF\u03b1 in the diseased joint and effectively prevented development of arthritis in a dose-dependent response fashion. Our results indicated that the TgTC mice represent a genetic model which can be used to comprehensively investigate the pathogenesis and therapeutics of TNF\u03b1-related diseases.<\/jats:p>","DOI":"10.1242\/bio.016279","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T02:53:14Z","timestamp":1458010394000},"page":"418-423","source":"Crossref","is-referenced-by-count":13,"title":["Establishment and evaluation of a transgenic mouse model of arthritis induced by overexpressing human tumor necrosis factor alpha"],"prefix":"10.1242","volume":"5","author":[{"given":"Ge","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, Guangdong 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu'e","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, Guangdong 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Jia","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, Guangdong 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Tang","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, Guangdong 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, Guangdong 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucai","family":"Peng","sequence":"additional","affiliation":[{"name":"Livzon MabPharm Inc., No. 38 Chuangye North Rd., Jinwan, Zhuhai, Guangdong 519045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, Guangdong 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"2021042423343630900_BIO016279C1","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1136\/annrheumdis-2012-202055","article-title":"C57BL\/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells","volume":"72","author":"Backlund","year":"2013","journal-title":"Ann. 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