Contractile properties of diaphragm muscle segments from old mdx and old transgenic mdx mice
Contractile properties of diaphragm muscle segments from old mdx and old transgenic mdx mice
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DOI：
10.1152/ajpcell.1997.272.6.c2063
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发表时间：
1997-06-01
影响因子：
5.5
通讯作者：
Faulkner, JA
中科院分区：
文献类型：
--
作者：
Lynch, GS;Rafael, JA;Faulkner, JA
年轻（4 至 6 个月大）mdx 小鼠的膈肌显示出严重的纤维坏死，其标准化力量和功率分别为对照 C57BL/10 小鼠值的 60% 和 46%。相比之下，用截短的肌营养不良蛋白小基因显微注射 mdx 小鼠胚胎产生了年轻的转基因 mdx (tg-mdx) 小鼠，其肌营养不良蛋白表达水平以及体外测量的膈肌条的结构和功能特性与对照小鼠没有不同。抗肌营养不良蛋白的表达和功能校正是否会在这些动物的一生中持续存在尚不清楚。我们测试了零假设，即在年老（24 个月）的 tg-mdx 小鼠中，肌营养不良蛋白表达充足，并且膈肌条的力量和功率与年轻 tg-mdx 小鼠或对照小鼠的膈肌条的值没有不同。与对照值相比，老 mdx 小鼠的膈肌条的归一化力和功率分别为 48% 和 31%。肌营养不良蛋白的表达在年老 tg-mdx 小鼠的膈肌中持续存在，并且功能特性与年轻 tg-mdx 或年轻或年老对照小鼠的膈肌没有不同。这些结果表明，通过转基因动物方法，肌营养不良蛋白的表达和功能校正在动物的一生中持续存在。
Diaphragm muscles of young (4- to 6-mo-old) mdx mice show severe fiber necrosis and have normalized forces and powers 60 and 46% of the values for control C57BL/10 mice. In contrast, microinjection of mdx mouse embryos with a truncated dystrophin minigene has produced young transgenic mdx (tg-mdx) mice with a level of dystrophin expression and structural and functional properties of diaphragm muscle strips measured in vitro not different from those of control mice. Whether dystrophin expression and functional corrections persist for the life span of these animals is not known. We tested the null hypothesis that, in old (24 mo) tg-mdx mice, dystrophin expression is adequate and diaphragm muscle strips have forces and powers not different from values for diaphragm muscle strips from young tg-mdx mice or control mice. Compared with control values, diaphragm muscle strips from old mdx mice had normalized forces and powers of 48 and 31%, respectively. Expression of dystrophin persisted in diaphragm muscles of old tg-mdx mice, and functional properties were not different from diaphragm muscles of young tg-mdx or young or old control mice. These results suggest that, with a transgenic animal approach, dystrophin expression and functional corrections persist for the life span of the animals.