腰骶髓发育异常是先天性肛门直肠畸形(ARMs)术后排便功能障碍的重要原因之一。课题组前期利用RNA-seq筛选到了转录因子Rbp-j及miR-342-5p在ARMs胎鼠腰骶髓中表达异常，预测发现Rbp-j是miR-342-5p的转录调节子。并且我们证明了miR-342-5p的一个新的靶基因，谷氨酸天冬氨酸转运体Glast。因此我们推测，下调的Rbp-j通过调节miR-342-5p转录，进而抑制Glast表达，破坏神经细胞间谷氨酸转运平衡而引起细胞的增殖、分化和凋亡异常，导致腰骶髓发育不良。本研究拟以Rbp-j/miR-342-5p/GLAST为主轴，利用乙烯硫脲致畸的ARMs大鼠模型以及Rbp-j转基因鼠，研究此通路各个因子间的调节关系，明确他们对细胞增殖、分化和凋亡的影响，为揭示ARMs胎鼠腰骶髓发育不良的机制提供重要的研究基础，并为临床治疗寻找新的干预靶点提供新思路。

The maldevelpopment of lumbosacral spinal cord in anorectal malformations (ARMs) plays a major role in the postoperative bowel dysfunction. Our preliminary studies revealed that the expression transcription factor Rbp-j decreased and the level of miR-342-5p increased in the ARMs fetuses by using RNA-seq. In addition, Rbp-j is predicted as a putative transcriptional regulator for miR-342-5p.We also identified glutamate aspartate transporter（Glast）as a new novel target gene of miR-342-5p. Based on our findings, we hypothesized that decreased Rbp-j suppressed Glast through regulating miR-342-5p, which destroyed the balance of glutamate aspartate transport and induce abnormal proliferation, differentiation and apoptosis, inducing to lumbosacral spinal cord dysplasia in ARMs fetuses. In the current study, we employ an ETU-induced ARMs rat model as well as Rbp-j transgenic rat model to investigate the relationship of Rbp-j/miR-342-5p/Glast, demonstrating the function and mechanism of this axis in proliferation, differentiation and apoptosis of lumbosacral spinal cord in ARMs. This project will provide scientific evidence for understanding for pathogenesis and new therapeutic treatments of lumbosacral spinal cord dysplasia in ARMs.