| pubmed-article:16115818 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C0026850 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C0056248 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C0445079 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C1413113 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C1514562 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C1883221 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C1705810 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C1883204 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:16115818 | lifeskim:mentions | umls-concept:C1880389 | lld:lifeskim |
| pubmed-article:16115818 | pubmed:issue | 19 | lld:pubmed |
| pubmed-article:16115818 | pubmed:dateCreated | 2005-9-16 | lld:pubmed |
| pubmed-article:16115818 | pubmed:abstractText | Human tibial muscular dystrophy and limb-girdle muscular dystrophy 2J are caused by mutations in the giant sarcomeric protein titin (TTN) adjacent to a binding site for the muscle-specific protease calpain 3 (CAPN3). Muscular dystrophy with myositis (mdm) is a recessive mouse mutation with severe and progressive muscular degeneration caused by a deletion in the N2A domain of titin (TTN-N2ADelta83), disrupting a putative binding site for CAPN3. To determine whether the muscular dystrophy in mutant mdm mice is caused by misregulation of CAPN3 activity, genetic crosses with CAPN3 overexpressing transgenic (C3Tg) and CAPN3 knockout (C3KO) mice were generated. Here, we report that overexpression of CAPN3 exacerbates the mdm disease, leading to a shorter life span and more severe muscular dystrophy. However, in a direct genetic test of CAPN3's role as a mediator of mdm pathology, C3KO;mdm double mutant mice showed no change in the progression or severity of disease indicating that aberrant CAPN3 activity is not a primary mechanism in this disease. To determine whether we could detect a functional deficit in titin in a non-disease state, we examined the treadmill locomotion of heterozygous +/mdm mice and detected a significant increase in stride time with a concomitant increase in stance time. Interestingly, these altered gait parameters were completely corrected by CAPN3 overexpression in transgenic C3Tg;+/mdm mice, supporting a CAPN3-dependent role for the N2A domain of TTN in the dynamics of muscle contraction. | lld:pubmed |
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| pubmed-article:16115818 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16115818 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16115818 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16115818 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16115818 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:16115818 | pubmed:issn | 0964-6906 | lld:pubmed |
| pubmed-article:16115818 | pubmed:author | pubmed-author:CoxGregory... | lld:pubmed |
| pubmed-article:16115818 | pubmed:author | pubmed-author:SeburnKevin... | lld:pubmed |
| pubmed-article:16115818 | pubmed:author | pubmed-author:SpencerMeliss... | lld:pubmed |
| pubmed-article:16115818 | pubmed:author | pubmed-author:HuebschKimber... | lld:pubmed |
| pubmed-article:16115818 | pubmed:author | pubmed-author:KudryashovaEl... | lld:pubmed |
| pubmed-article:16115818 | pubmed:author | pubmed-author:WooleyChristi... | lld:pubmed |
| pubmed-article:16115818 | pubmed:author | pubmed-author:SherRoger BRB | lld:pubmed |
| pubmed-article:16115818 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16115818 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:16115818 | pubmed:volume | 14 | lld:pubmed |
| pubmed-article:16115818 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16115818 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16115818 | pubmed:pagination | 2801-11 | lld:pubmed |
| pubmed-article:16115818 | pubmed:dateRevised | 2011-3-9 | lld:pubmed |
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