{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:27:46Z","timestamp":1784154466733,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T00:00:00Z","timestamp":1476316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21NS088691"],"award-info":[{"award-number":["R21NS088691"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54AR065139"],"award-info":[{"award-number":["U54AR065139"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32HL007828"],"award-info":[{"award-number":["T32HL007828"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,12,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Duchenne muscular dystrophy (DMD) is a severe, degenerative muscle disease that is commonly studied using the <jats:italic>mdx<\/jats:italic> mouse. The <jats:italic>mdx<\/jats:italic> diaphragm muscle closely mimics the pathophysiological changes in DMD muscles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>mdx<\/jats:italic> diaphragm force is commonly assessed <jats:italic>ex vivo<\/jats:italic>, precluding time course studies. Here we used ultrasonography to evaluate time\u2010dependent changes in diaphragm function <jats:italic>in vivo<\/jats:italic>, by measuring diaphragm movement amplitude.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In <jats:italic>mdx<\/jats:italic> mice, diaphragm amplitude decreased with age and values were much lower than for wild\u2010type mice. Importantly, diaphragm amplitude strongly correlated with <jats:italic>ex vivo<\/jats:italic> specific force values.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Micro\u2010dystrophin administration increased <jats:italic>mdx<\/jats:italic> diaphragm amplitude by 26% after 4\u00a0weeks. Diaphragm amplitude correlated positively with <jats:italic>ex vivo<\/jats:italic> force values and negatively with diaphragm fibrosis, a major cause of DMD muscle weakness.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These studies validate diaphragm ultrasonography as a reliable technique for assessing time\u2010dependent changes in <jats:italic>mdx<\/jats:italic> diaphragm function <jats:italic>in vivo<\/jats:italic>. This technique will be valuable for testing potential therapies for DMD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a severe, degenerative muscle disease caused by dystrophin mutations. The <jats:italic>mdx<\/jats:italic> mouse is a widely used animal model of DMD. The <jats:italic>mdx<\/jats:italic> diaphragm muscle most closely recapitulates key features of DMD muscles, including progressive fibrosis and considerable force loss. Diaphragm function in <jats:italic>mdx<\/jats:italic> mice is commonly evaluated by specific force measurements <jats:italic>ex vivo<\/jats:italic>. While useful, this method only measures force from a small muscle sample at one time point. Therefore, accurate assessment of diaphragm function <jats:italic>in vivo<\/jats:italic> would provide an important advance to study the time course of functional decline and treatment benefits. Here, we evaluated an ultrasonography technique for measuring time\u2010dependent changes of diaphragm function in <jats:italic>mdx<\/jats:italic> mice. Diaphragm movement amplitude values for <jats:italic>mdx<\/jats:italic> mice were considerably lower than those for wild\u2010type, decreased from 8 to 18\u00a0months of age, and correlated strongly with <jats:italic>ex vivo<\/jats:italic> specific force. We then investigated the time course of diaphragm amplitude changes following administration of an adeno\u2010associated viral vector expressing Flag\u2010micro\u2010dystrophin (AAV\u2010\u03bcDys) to young adult <jats:italic>mdx<\/jats:italic> mice. Diaphragm amplitude peaked 4\u00a0weeks after AAV\u2010\u03bcDys administration, and was 26% greater than control <jats:italic>mdx<\/jats:italic> mice at this time. This value decreased slightly to 21% above <jats:italic>mdx<\/jats:italic> controls after 12\u00a0weeks of treatment. Importantly, diaphragm amplitude again correlated strongly with <jats:italic>ex vivo<\/jats:italic> specific force. Also, diaphragm amplitude and specific force negatively correlated with fibrosis levels in the muscle. Together, our results validate diaphragm ultrasonography as a reliable technique for assessing time\u2010dependent changes in dystrophic diaphragm function <jats:italic>in vivo<\/jats:italic>, and for evaluating potential therapies for DMD.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272707","type":"journal-article","created":{"date-parts":[[2016,8,29]],"date-time":"2016-08-29T02:23:10Z","timestamp":1472437390000},"page":"7215-7227","source":"Crossref","is-referenced-by-count":34,"title":["Validation of ultrasonography for non\u2010invasive assessment of diaphragm function in muscular dystrophy"],"prefix":"10.1113","volume":"594","author":[{"given":"Nicholas P.","family":"Whitehead","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Bible","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy L.","family":"Odom","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Washington  Seattle WA 98195 USA"},{"name":"Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin E.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley C.","family":"Froehner","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington  Seattle WA 98195 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00007.2015"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(02)00003-2"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000958"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001950"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11632"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.02.006"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.07.016"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60025-3"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181aa31c2"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-005-1433-7"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04865.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0302-253"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61737-982-6_1"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.02.002"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23172"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241508198"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4054"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3710"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.265.3.C834"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002147"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1517\/21678707.2015.1088780"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv466"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24294"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23671"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652312800840603"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.213"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/352536a0"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24675"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90463-1"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509536112"},{"key":"e_1_2_5_32_1","first-page":"e51290","article-title":"Diagnostic ultrasound imaging of mouse diaphragm function","author":"Zuo L","year":"2014","journal-title":"J Vis Exp"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP272707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP272707","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP272707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T10:50:59Z","timestamp":1696157459000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP272707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,13]]},"references-count":31,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2016,12,15]]}},"alternative-id":["10.1113\/JP272707"],"URL":"https:\/\/doi.org\/10.1113\/jp272707","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,13]]}}}