{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:03:00Z","timestamp":1791118980383,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,2,21]],"date-time":"2014-02-21T00:00:00Z","timestamp":1392940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes of Arthritis, Musculoskeletal and Skin Diseases at the National Institutes of Health","award":["AR-048816"],"award-info":[{"award-number":["AR-048816"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Loss of slow skeletal muscle troponin T (ssTnT) due to a nonsense mutation in codon Glu<jats:sup>180<\/jats:sup> causes a lethal form of recessively inherited nemaline myopathy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We studied the phenotypes of partial and total loss of ssTnT in the diaphragm and soleus muscles of <jats:italic>Tnnt1<\/jats:italic> gene targeted mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ssTnT deficiency resulted in significant decreases in other slow fibre\u2010specific myofilament proteins whereas fast fibre\u2010specific myofilament proteins were increased correspondingly.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ssTnT deficiency produced significantly smaller type I slow fibres and compensatory growth of type II fast fibres with significantly reduced contractile force and tolerance to fatigue.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ssTnT\u2010deficient soleus muscle exhibited a significant numbers of small\u2010sized central nuclei type I fibres, indicating regeneration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The data support the critical role of ssTnT in skeletal muscle function and the causal effect of its loss on the pathogenesis of nemaline myopathy.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The total loss of slow skeletal muscle troponin T (ssTnT encoded by <jats:italic>TNNT1<\/jats:italic> gene) due to a nonsense mutation in codon Glu<jats:sup>180<\/jats:sup> causes a lethal form of recessively inherited nemaline myopathy (Amish nemaline myopathy, ANM). To investigate the pathogenesis and muscle pathophysiology of ANM, we studied the phenotypes of partial and total loss of ssTnT in <jats:italic>Tnnt1<\/jats:italic> gene targeted mice. An insertion of neomycin resistance cassette in intron 10 of <jats:italic>Tnnt1<\/jats:italic> gene caused an approximately 60% decrease in ssTnT protein expression whereas <jats:italic>cre<\/jats:italic>\u2010<jats:italic>lox<\/jats:italic>P\u2010mediated deletion of exons 11\u201313 resulted in total loss of ssTnT, as seen in ANM muscles. In diaphragm and soleus muscles of the knockdown and knockout mouse models, we demonstrated that ssTnT deficiency resulted in significantly decreased levels of other slow fibre\u2010specific myofilament proteins whereas fast fibre\u2010specific myofilament proteins were increased correspondingly. Immunohistochemical studies revealed that ssTnT deficiency produced significantly smaller type I slow fibres and compensatory growth of type II fast fibres. Along with the slow fibre atrophy and the changes in myofilament protein isoform contents, ssTnT deficiency significantly reduced the tolerance to fatigue in soleus muscle. ssTnT\u2010deficient soleus muscle also contains significant numbers of small\u2010sized central nuclei type I fibres, indicating active regeneration. The data provide strong support for the essential role of ssTnT in skeletal muscle function and the causal effect of its loss in the pathology of ANM. This observation further supports the hypothesis that the function of slow fibres can be restored in ANM patients if a therapeutic supplement of ssTnT is achieved.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2013.268177","type":"journal-article","created":{"date-parts":[[2014,1,21]],"date-time":"2014-01-21T03:34:40Z","timestamp":1390275280000},"page":"1367-1380","source":"Crossref","is-referenced-by-count":39,"title":["Deficiency of slow skeletal muscle troponin T causes atrophy of type I slow fibres and decreases tolerance to fatigue"],"prefix":"10.1113","volume":"592","author":[{"given":"Bin","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Physiology Wayne State University School of Medicine  Detroit MI 48201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingru","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Physiology Wayne State University School of Medicine  Detroit MI 48201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010P.","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Physiology Wayne State University School of Medicine  Detroit MI 48201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00422.2005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022066922922"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-009-9202-0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.2144\/03346bm03","article-title":"Optimized vector for conditional gene targeting in mouse embryonic stem cells","volume":"34","author":"Conrad M","year":"2003","journal-title":"Biotechniques"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.020826"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.1.49"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00051-7"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801163200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303469200"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.4.C1067"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v18.i2.10"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/301604"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/303089"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00110.2008"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-136"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005397501968"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413696200"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.10.013"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.261.2.C195"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00462.2006"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2013.268177","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2013.268177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:55:43Z","timestamp":1696035343000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2013.268177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,21]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,3,15]]}},"alternative-id":["10.1113\/jphysiol.2013.268177"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2013.268177","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,21]]}}}