Mutation types and aging differently affect revertant fiber expansion in dystrophic mdx and mdx52 mice.
Mutation types and aging differently affect revertant fiber expansion in dystrophic mdx and mdx52 mice.
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DOI：
10.1371/journal.pone.0069194
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yokota T
中科院分区：
文献类型：
--
作者：
Echigoya Y;Lee J;Rodrigues M;Nagata T;Tanihata J;Nozohourmehrabad A;Panesar D;Miskew B;Aoki Y;Yokota T
Duchenne型肌营养不良症（DMD）是最常见和致命的遗传性疾病之一，mdx小鼠肌病是由缺乏肌营养不良蛋白引起的。这些营养不良的肌肉含有零星的肌营养不良蛋白表达的回复突变纤维（RF）的集群，如通过免疫组织化学检测。已知RF产生于具有自发外显子跳跃（选择性剪接）的肌肉前体细胞，并且通过肌肉变性/再生过程随着年龄的增加克隆地扩大大小。回复突变簇的扩增被认为代表了肌肉再生和这种前体细胞增殖的累积历史。然而，RF产生和扩展的确切机制知之甚少。在这里，为了测试突变类型和年龄对RF扩展和肌肉再生的影响，我们检查了具有相同C57 BL/6背景的mdx小鼠（外显子23中含有无义突变）和mdx 52小鼠（外显子52中含有缺失突变）在2、6、12和18月龄时的RF数量。在所有年龄组中，与mdx 52小鼠相比，Mdx小鼠显示出显著更高数量的RF，这表明回复突变体纤维扩张在很大程度上取决于基因中的突变类型和/或位置。与mdx 52小鼠相比，mdx小鼠在6月龄时RF的表达和聚集水平显著增加。与RF随着年龄的增加而显着扩张相反，两种小鼠品系的中央有核纤维和胚胎肌球蛋白重链阳性纤维（分别指示累积和当前肌肉再生）的数量随着年龄的增长而减少。这些结果表明，突变类型和老化不同地影响mdx和mdx 52小鼠的回复突变纤维扩张。
Duchenne muscular dystrophy (DMD), one of the most common and lethal genetic disorders, and the mdx mouse myopathies are caused by a lack of dystrophin protein. These dystrophic muscles contain sporadic clusters of dystrophin-expressing revertant fibers (RFs), as detected by immunohistochemistry. RFs are known to arise from muscle precursor cells with spontaneous exon skipping (alternative splicing) and clonally expand in size with increasing age through the process of muscle degeneration/regeneration. The expansion of revertant clusters is thought to represent the cumulative history of muscle regeneration and proliferation of such precursor cells. However, the precise mechanisms by which RFs arise and expand are poorly understood. Here, to test the effects of mutation types and aging on RF expansion and muscle regeneration, we examined the number of RFs in mdx mice (containing a nonsense mutation in exon 23) and mdx52 mice (containing deletion mutation of exon 52) with the same C57BL/6 background at 2, 6, 12, and 18months of age. Mdx mice displayed a significantly higher number of RFs compared to mdx52 mice in all age groups, suggesting that revertant fiber expansion largely depends on the type of mutation and/or location in the gene. A significant increase in the expression and clustering levels of RFs was found beginning at 6months of age in mdx mice compared with mdx52 mice. In contrast to the significant expansion of RFs with increasing age, the number of centrally nucleated fibers and embryonic myosin heavy chain-positive fibers (indicative of cumulative and current muscle regeneration, respectively) decreased with age in both mouse strains. These results suggest that mutation types and aging differently affect revertant fiber expansion in mdx and mdx52 mice.
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影响因子：
3.5
作者：
GORECKI, DC;MONACO, AP;BARNARD, PJ
通讯作者：
BARNARD, PJ
影响因子：
3.5
作者：
DSOUZA, VN;MAN, NT;RAY, PN
通讯作者：
RAY, PN
DOI：
10.1186/1479-0556-4-3
发表时间：
2006-05-24
期刊：
Genetic vaccines and therapy
影响因子：
--
作者：
Fall, Abbie M;Johnsen, Russell;Wilton, Stephen D
通讯作者：
Wilton, Stephen D
影响因子：
30.8
作者：
BYERS, TJ;LIDOV, HGW;KUNKEL, LM
通讯作者：
KUNKEL, LM
影响因子：
5.6
作者：
Bhasin, N;Law, R;Discher, DE
通讯作者：
Discher, DE