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Longitudinal and cross\u2010sectional pathologic outcomes in the musculoskeletal and cardiopulmonary systems were assessed via ultrasound, micro\u2013computed tomography, grip strength measurements, histologic and serologic analyses, flow cytometry, and skeletal muscle physiologic measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to male Tg3647 mice (n = 30), female Tg3647 mice (n = 34) had significantly shorter lifespans (<jats:italic>P<\/jats:italic> &lt; 0.001) and exhibited the following pathologic features (n = 4\u20136 per group; <jats:italic>P<\/jats:italic> &lt; 0.05 versus male Tg3647 littermates): gross deficits in body mass and muscle weight, early\u2010onset inflammatory arthritis with severity of end\u2010stage arthritis that was as severe as that seen in male transgenic mice, and early onset and increased severity of inflammatory interstitial lung disease (<jats:styled-content style=\"fixed-case\">ILD<\/jats:styled-content>). Histologically, the <jats:styled-content style=\"fixed-case\">ILD<\/jats:styled-content> observed in Tg3647 mice was characterized by inflammatory cell accumulation and pulmonary arteriole thickening, which was concomitant with the presence of right ventricular hypertrophy, a feature that was also more severe in the female compared to male Tg3647 mice (<jats:italic>P<\/jats:italic> &lt; 0.05). No sexual dimorphisms in <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010induced deficient grip strength, axial skeletal growth, or bone loss were found. Globally, the extent of the pathologic changes observed in female Tg3647 mice was greater than that observed in male Tg3647 mice when each group was compared to their sex\u2010matched <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> littermates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings indicate that <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> selectively drives the early onset of arthritis and progression of pathologic changes in the cardiopulmonary system in female Tg3647 mice. These results in the Tg3647 mouse identify it as a suitable model to better understand the mechanisms underlying sexual dimorphism and cardiopulmonary disease in the setting of inflammatory arthritis and other connective tissue diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40903","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T07:40:22Z","timestamp":1554882022000},"page":"1512-1523","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Selective Sexual Dimorphisms in Musculoskeletal and Cardiopulmonary Pathologic Manifestations and Mortality Incidence in the Tumor Necrosis Factor\u2013Transgenic Mouse Model of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"71","author":[{"given":"Richard D.","family":"Bell","sequence":"first","affiliation":[{"name":"University of Rochester Medical Center  Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily K.","family":"Wu","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center  Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Rudmann","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center  Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Forney","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center  Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire R. 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