INSERM/UEVE UMR 861, I-STEM AFM, 5 rue H. Desbruères, Evry Cedex, France.
Cell Stem Cell. 2011 Apr 8;8(4):434-44. doi: 10.1016/j.stem.2011.02.004. Epub 2011 Mar 31.
Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting a variety of organs, including the central nervous system. By using neuronal progeny derived from human embryonic stem cells carrying the causal DM1 mutation, we have identified an early developmental defect in genes involved in neurite formation and the establishment of neuromuscular connections. Differential gene expression profiling and quantitative RT-PCR revealed decreased expression of two members of the SLITRK family in DM1 neural cells and in DM1 brain biopsies. In addition, DM1 motoneuron/muscle cell cocultures showed alterations that are consistent with the known role of SLITRK genes in neurite outgrowth, neuritogenesis, and synaptogenesis. Rescue and knockdown experiments suggested that the functional defects can be directly attributed to SLITRK misexpression. These neuropathological mechanisms may be clinically significant for the functional changes in neuromuscular connections associated with DM1.
肌强直性营养不良 1 型（DM1）是一种多系统疾病，影响多种器官，包括中枢神经系统。通过使用携带致病 DM1 突变的人胚胎干细胞衍生的神经元祖细胞，我们已经确定了涉及轴突形成和建立神经肌肉连接的基因的早期发育缺陷。差异基因表达谱和定量 RT-PCR 显示，DM1 神经细胞和 DM1 脑活检中 SLITRK 家族的两个成员的表达降低。此外，DM1 运动神经元/肌肉细胞共培养显示出与 SLITRK 基因在轴突生长、神经发生和突触发生中的已知作用一致的改变。挽救和敲低实验表明，功能缺陷可直接归因于 SLITRK 表达错误。这些神经病理学机制对于与 DM1 相关的神经肌肉连接的功能变化可能具有临床意义。
