神经肌肉接头(NMJ)是运动神经元和骨骼肌之间的突触，负责神经系统与肌纤维之间的信息传递。肌肉萎缩和衰老同时也伴随着NMJ结构和功能的退化，但其机制尚不清楚。我们利用RNAseq发现胶原蛋白6（Collagen 6,Col6）基因表达在老龄鼠NMJ显著下降，并在蛋白水平也得到验证。有意思的是Col6是先天性肌肉萎缩症的致病基因，特别是我们在成年鼠肌肉上利用CRISPR敲除Col6后NMJ呈现片段化等老化形态。因此，我们推测Col6可能是NMJ功能维持和老化的重要蛋白。本项目拟首先研究Col6蛋白缺失小鼠NMJ结构和功能变化及其分子机制，然后在转基因小鼠上研究Col6诱导表达是否延缓NMJ的老化。本项目结果将为探讨突触功能和维持提供重要线索，也为老年型肌营养不良综合症等奠定理论依据。

The NMJ is a synapse between motor neuron terminals and skeletal muscle fibers that transmit signals from nerve system to muscle fibers. Muscle atrophy and aging is accompanied by a deterioration of the structure and function of NMJ,however, the molecular mechanism remains unclear. Using RNAseq, we found that collagen protein 6 (Col6) was significantly decreased in NMJ synaptic regions of aged mice, and also confirmed on protein level. What's interesting is that Col6 is a causative gene for congenital muscular dystrophy, especially, NMJs showed fragmented when Col6 were knockout using CRISPR in adult mice. We hypothesized that Col6 was a key protein for NMJ maintenance and senescence. In this study, firstly we will study the deterioration of the structure and function of NMJ in Col6 mutant mice and their molecular mechanisms. Then, we will generate imCol6 transgenic mice to determine whether enhancing Col6 in aged mice mitigates NMJ senescence. The results of this study will not only provide the clues to investigate the function and maintenance of synapse in nerve system, but also lay a theoretical basis for age related muscular dystrophy syndrome.