{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:02:58Z","timestamp":1791118978950,"version":"4.1.0"},"reference-count":33,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:p> A complex rearrangement mutation in the mouse titin gene leads to an in-frame 83-amino acid deletion in the N2A region of titin. Autosomal recessive inheritance of the titin muscular dystrophy with myositis ( Ttn<jats:sup> mdm\/mdm<\/jats:sup>) mutation leads to a severe early-onset muscular dystrophy and premature death. We hypothesized that the N2A deletion would negatively impact the force-generating capacity and passive mechanical properties of the mdm diaphragm. We measured in vitro active isometric contractile and passive length-tension properties to assess muscle function at 2 and 6 wk of age. Micro-CT, myosin heavy chain Western blotting, and histology were used to assess diaphragm structure. Marked chest wall distortions began at 2 wk and progressively worsened until 5 wk. The percentage of myofibers with centrally located nuclei in mdm mice was significantly ( P &lt; 0.01) increased at 2 and 6 wk by 4% and 17%, respectively, compared with controls. At 6 wk, mdm diaphragm twitch stress was significantly ( P &lt; 0.01) reduced by 71%, time to peak twitch was significantly ( P &lt; 0.05) reduced by 52%, and half-relaxation time was significantly ( P &lt; 0.05) reduced by 57%. Isometric tetanic stress was significantly ( P &lt; 0.05) depressed in 2- and 6-wk mdm diaphragms by as much as 64%. Length-tension relationships of the 2- and 6-wk mdm diaphragms showed significantly ( P &lt; 0.05) decreased extensibility and increased stiffness. Slow myosin heavy chain expression was aberrantly favored in the mdm diaphragm at 6 wk. Our data strongly support early contractile and passive mechanical aberrations of the respiratory pump in mdm mice. <\/jats:p>","DOI":"10.1152\/ajpcell.16.2008","type":"journal-article","created":{"date-parts":[[2008,8,28]],"date-time":"2008-08-28T00:46:10Z","timestamp":1219884370000},"page":"C1092-C1102","source":"Crossref","is-referenced-by-count":35,"title":["Early mechanical dysfunction of the diaphragm in the muscular dystrophy with myositis (<i>Ttn<\/i><sup><i>mdm<\/i><\/sup>) model"],"prefix":"10.1152","volume":"295","author":[{"given":"Michael A.","family":"Lopez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia S.","family":"Pardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aladin M.","family":"Boriek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Boriek AM, Liu S, Rodarte JR. 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