Suzuki Naoki, Aoki Masashi, Hinuma Yuji, Takahashi Toshiaki, Onodera Yoshiaki, Ishigaki Aya, Kato Masaaki, Warita Hitoshi, Tateyama Maki, Itoyama Yasuto
Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan.
Neurosci Res. 2005 May;52(1):47-60. doi: 10.1016/j.neures.2005.01.006.
The SJL mouse is a model for human dysferlinopathy (limb-girdle muscular dystrophy type 2B and Miyoshi myopathy). We used cDNA microarrays to compare the expression profiles of 10,012 genes in control and SJL quadriceps femoris muscles in order to find genes involved in the degeneration and regeneration process and in dysferlin's functional network. Many genes involved in the process of muscle regeneration are observed to be up-regulated in SJL mice, including cardiac ankyrin repeated protein (CARP), Neuraminidase 2, interleukin-6, insulin-like growth factor-2 and osteopontin. We found the upregulation of S100 calcium binding proteins, neural precursor cell expressed, developmentally down-regulated gene 4-like (NEDD4L) with C2 domain, and intracellular protein traffic associated proteins (Rab6 and Rab2). These proteins have the potential to interact with dysferlin. We must reveal some other molecules which may work with dysferlin in order to clarify the pathological network of dysferlinopathy. This process may lead to future improvements in the therapy for human dysferlinopathy.
SJL小鼠是人类dysferlin病（2B型肢带型肌营养不良症和宫下肌病）的一种模型。我们使用cDNA微阵列比较了对照和SJL股四头肌中10012个基因的表达谱，以寻找参与变性和再生过程以及dysferlin功能网络的基因。观察到许多参与肌肉再生过程的基因在SJL小鼠中上调，包括心肌锚蛋白重复蛋白（CARP）、神经氨酸酶2、白细胞介素-6、胰岛素样生长因子-2和骨桥蛋白。我们发现了S100钙结合蛋白、神经前体细胞表达的发育下调基因4样蛋白（NEDD4L）（带有C2结构域）以及细胞内蛋白质运输相关蛋白（Rab6和Rab2）的上调。这些蛋白质有可能与dysferlin相互作用。为了阐明dysferlin病的病理网络，我们必须揭示一些可能与dysferlin协同作用的其他分子。这一过程可能会带来未来人类dysferlin病治疗方法的改进。
