Zhou Lan, Rafael-Fortney Jill A, Huang Ping, Zhao Xinyu S, Cheng Georgiana, Zhou Xiaohua, Kaminski Henry J, Liu Liping, Ransohoff Richard M
Department of Neurology, Cleveland Clinic, Cleveland, OH 44195, USA.
J Neurol Sci. 2008 Jan 15;264(1-2):106-11. doi: 10.1016/j.jns.2007.08.029. Epub 2007 Sep 24.
To address whether mdx mice with haploinsufficiency of utrophin (mdx/utrn+/-) develop more severe skeletal muscle inflammation and fibrosis than mdx mice, to represent a better model for Duchenne muscular dystrophy (DMD), we performed qualitative and quantitative analysis of skeletal muscle inflammation and fibrosis in mdx and mdx/utrn+/- littermates. Inflammation was significantly worse in mdx/utrn+/- quadriceps at age 3 and 6 months and in mdx/utrn+/- diaphragm at age 3 but not 6 months. Fibrosis was more severe in mdx/utrn+/- diaphragm at 6 months, and at this age, mild fibrosis was noted in quadriceps of mdx/utrn+/- but not mdx mice. The findings indicate that utrophin compensates, although insufficiently, for the effects of dystrophin loss with regard to inflammation and fibrosis of both quadriceps and diaphragm muscles in mdx mice. With more severe muscle dystrophy than mdx mice and a longer life span than utrophin-dystrophin-deficient (dko) mice, mdx/utrn+/- mice provide a better mouse model for testing potential therapies for muscle inflammation and fibrosis associated with DMD.
为了探究肌动蛋白缺乏的mdx小鼠（mdx/utrn+/-）是否比mdx小鼠发展出更严重的骨骼肌炎症和纤维化，从而成为杜氏肌营养不良症（DMD）的更好模型，我们对mdx和mdx/utrn+/-同窝小鼠的骨骼肌炎症和纤维化进行了定性和定量分析。在3个月和6个月大时，mdx/utrn+/-股四头肌的炎症明显更严重；在3个月大时，mdx/utrn+/-膈肌的炎症也更严重，但6个月大时则不然。6个月大时，mdx/utrn+/-膈肌的纤维化更严重，且在这个年龄，mdx/utrn+/-股四头肌出现轻度纤维化，而mdx小鼠的股四头肌未出现。这些发现表明，在mdx小鼠中，就股四头肌和膈肌的炎症及纤维化而言，肌动蛋白虽不能充分补偿肌营养不良蛋白缺失的影响，但仍有一定补偿作用。mdx/utrn+/-小鼠的肌肉营养不良比mdx小鼠更严重，寿命比肌动蛋白-肌营养不良蛋白双缺陷（dko）小鼠更长，为测试与DMD相关的肌肉炎症和纤维化的潜在治疗方法提供了更好的小鼠模型。
