sc1在中枢神经系统髓鞘形成中的作用
Role of Tsc1 during myelination in the Central Nervous System
目的：研究Tsc1(Tuberous Sclerosis 1)在少突胶质细胞发育、分化、成熟以及中枢神经系统髓鞘形成中的作用。 方法： 将Olig1cre与Tsc1被锁定的转基因小鼠（Tsc1c/c）杂交，在少突胶质细胞系中特异性敲除Tsc1基因。通过免疫荧光染色、核酸原位杂交、电子显微镜等分析小鼠表型并进一步用RNA-seq检测下游基因表达的变化。 结果：Tsc1c/c;Olig1cre小鼠（突变组）约P20出现全身震颤、共济失调等行为学异常，成熟少突胶质细胞标记物MBP、PLP和CC1在发育期的表达明显低于对照组且持续至成年期，表明少突胶质细胞成熟障碍；视神经电子显微镜显示，P14和P25的髓鞘数量明显少于对照组，表明中枢神经系统髓鞘形成不良；少突胶质细胞系标志物Olig2和前体细胞（OPCs）标志物PDGFRα表达明显低于对照组，而PDGFRα＋细胞数／Olig2＋细胞数百分比升高，表明少突胶质细胞分化受阻。 结论：Tsc1是少突胶质细胞生成、分化、成熟和中枢神经系统髓鞘形成所必需的。
Objective To evaluate the Tsc1 in oligodendrocyte development during myelination in the Centrol Nervous System. Methods Conditional Sip1flox/flox mice were bred with an Olig1-Cre line, in which Cre recombinase is produced in the oligodendrocyte lineage.Analyze the the phenotypes of mice by using the immunocytochemistry, the in situ hybridization and the electron micrographs. Results The mutant mice, but not their control littermates, developed generalized tremors and ataxia from postnatal day 20. Expression of MBP,PLP and CC1 decreased in the mutant mice, which is a sign of dysgenesis of myelin. In contrast to a large number of myelinated axons that are observed in control mice at P14 and P25, they decreased in the optic nerve of mutants,indicating deficiency in myelin formation in the central nervous system. The expression of Olig2 and PDGFRα decreased and the percent of PDGFRα+cells/ Olig2+cells increased in mutant mice, showing defects in oligodendrocytes differentiation. Conclusion Tsc1 is required for genesis, differentiation and maturation of oligodendrocytes and myelination in central nervous system.
刘蕾、童煜、毛萌
基础医学神经病学、精神病学分子生物学
sc1少突胶质细胞髓鞘形成
sc1oligodendrocytemyelination
刘蕾,童煜,毛萌.sc1在中枢神经系统髓鞘形成中的作用[EB/OL].(2016-07-11)[2025-08-18].http://www.paper.edu.cn/releasepaper/content/201607-125.点此复制
评论