Kobayashi Kinji, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji
Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka 598-8531, Japan.
Exp Toxicol Pathol. 2010 Sep;62(5):509-17. doi: 10.1016/j.etp.2009.06.009. Epub 2009 Jul 16.
The pathogenesis of limb-girdle muscular dystrophy type 2B (LGMD2B) dysferlinopathy remains to be investigated. The distribution and characterization of skeletal muscle lesions were examined in two different LGMD2B mouse models, SJL and A/J mice (at 10 and 35 weeks old), in association with the endoplasmic reticulum (ER) stress. SJL mice showed an earlier age of onset and a faster progression of skeletal muscle lesions as compared with those of A/J mice; the sensitivity difference to muscular dystrophic lesions between SJL and A/J mice was observed in the lumbar muscles (particularly, lumbar longissimus and sublumbar muscles); the lesions seen mainly in SJL mice at 35 weeks old consisted of degeneration, necrosis, fatty infiltration, variation in muscle fiber size and atrophy in muscle fibers. Enzyme-histochemically, the fast-twitch muscle fiber was predominant for the degenerative changes seen in the rectus femoris and lateral longissimus muscles of SJL mice. Immunohistochemically, the main reactive cell type observed in and around degenerative and/or necrotic muscle fibers was macrophages, demonstrable with an anti-F4/80 antibody. Because the analyses of spliced XBP1 mRNA, a marker of ER stress, did not show the increased expression, it was considered that ER stress did not affect the progression of skeletal muscle lesions in SJL mice with the advanced stage of dysferlinopathy.
2B型肢带型肌营养不良（LGMD2B）相关的dysferlinopathy的发病机制仍有待研究。在两种不同的LGMD2B小鼠模型SJL和A/J小鼠（10周龄和35周龄）中，结合内质网（ER）应激，检查骨骼肌病变的分布和特征。与A/J小鼠相比，SJL小鼠的发病年龄更早，骨骼肌病变进展更快；在腰大肌（特别是腰最长肌和腰下肌）中观察到SJL和A/J小鼠对肌营养不良性病变的敏感性差异；35周龄的SJL小鼠中主要出现的病变包括变性、坏死、脂肪浸润、肌纤维大小变化和肌纤维萎缩。酶组织化学分析显示，在SJL小鼠的股直肌和外侧最长肌中，快速收缩肌纤维是主要发生退行性变化的肌纤维类型。免疫组织化学分析显示，在变性和/或坏死肌纤维及其周围观察到的主要反应细胞类型是巨噬细胞，用抗F4/80抗体可证实。由于内质网应激标志物剪接的XBP1 mRNA分析未显示表达增加，因此认为内质网应激不影响处于dysferlinopathy晚期的SJL小鼠骨骼肌病变的进展。
