Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber atrophy.
Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber atrophy.
复制标题
DOI：
10.1242/dmm.019430
复制
发表时间：
2015-06
影响因子：
4.3
通讯作者：
Xu T
中科院分区：
文献类型：
--
作者：
Tian L;Ding S;You Y;Li TR;Liu Y;Wu X;Sun L;Xu T
Nemaline myopathy (NM) is one of the most common forms of congenital myopathy, and affects either fast myofibers, slow myofibers, or both. However, an animal model for congenital myopathy with fast-myofiber-specific atrophy is not available. Furthermore, mutations in the leiomodin-3 (LMOD3) gene have recently been identified in a group of individuals with NM. However, it is not clear how loss of LMOD3 leads to NM. Here, we report a mouse mutant in which the piggyBac (PB) transposon is inserted into the Lmod3 gene and disrupts its expression. Lmod3PB/PB mice show severe muscle weakness and postnatal growth retardation. Electron microscopy and immunofluorescence studies of the mutant skeletal muscles revealed the presence of nemaline bodies, a hallmark of NM, and disorganized sarcomeric structures. Interestingly, Lmod3 deficiency caused muscle atrophy specific to the fast fibers. Together, our results show that Lmod3 is required in the fast fibers for sarcomere integrity, and this study offers the first NM mouse model with muscle atrophy that is specific to fast fibers. This model could be a valuable resource for interrogating myopathy pathogenesis and developing therapeutics for NM as well as other pathophysiological conditions with preferential atrophy of fast fibers, including cancer cachexia and sarcopenia. Highlighted Article: A leiomodin-3 mouse mutant generated by insertion of the piggyBac transposon exhibits nemaline myopathy with fast-myofiber-specific atrophy.
登录
查看更多内容
影响因子：
15.9
作者：
Cenik, Bercin K.;Garg, Ankit;Liu, Ning
通讯作者：
Liu, Ning
影响因子：
4
作者：
Nworu, Chinedu U.;Kraft, Robert;Krieg, Paul A.
通讯作者：
Krieg, Paul A.
影响因子：
11.2
作者：
Ryan, MM;Schnell, C;North, KN
通讯作者：
North, KN
影响因子：
3.4
作者：
Olive, Montse;Goldfarb, Lev G.;Sambuughin, Nyamkhishig
通讯作者：
Sambuughin, Nyamkhishig
影响因子：
64.5
作者：
Ding, S;Wu, XH;Xu, T
通讯作者：
Xu, T