中文摘要：

目的：了解FMR1基因敲除小鼠脑组织中突触素Ⅰ（SYN）表达的改变，以探讨脆性X综合征的发病机制。方法：将40只小鼠按基因型及年龄组的不同分为：1周龄基因敲除型组（KO^1W组）、1周龄野生型组（WT^1W组1、6周龄基因敲除型组（KO^6W组）、6周龄野生型组（WT^6W组）4组，每组10只。取小鼠脑组织用免疫组织化学法检测SYN的分布和表达。用图象分析仪采集各脑区的平均光密度值（MOD），分析不同基因型及不同年龄组SYN在各脑区MOD值的差异。结果：按基因型分析，KO型小鼠大脑皮质SYN的表达均较WT型小鼠显著降低（P〈0．01）；但在苔藓纤维层，新生KO小鼠SYN的表达较其WT型显著增高（P〈0．01）。按年龄组分析，KO^1W组小鼠中的SYN在各脑区的表达较KO^6W高（P〈0．05），在大脑皮质及苔藓纤维层（P〈0．01）处比在CA1区（P〈0．05）更明显：WT^1W组SYN的表达在皮质及CAl区高于WT^6W组（P〈0．01），但在苔藓纤维层却比WT^6W组低（P〈0．01）。结论：FMR1基因敲除小鼠大脑皮质突触数量减少而新生期海马苔藓纤维层突触数量异常增多，可能与患者智能低下、神经兴奋性增高有关。

英文摘要：

Objective： To explore the altered synapsin I（SYN） expression in brain tissues of FMRl-knockout mice for a better pathogenetic understanding of fragile X syndrome. Methods： Forty mice were allocated to 4 groups （n=10 each） based on their ages and genotypes, namely, FMR1 -knockout mice at 1 week or 6 weeks of life （KO^1w group and KO^6w group） and wild-type gene nfice at 1 week or 6 weeks of life （WT^1w group and WT^6W group）. The distribution and expression of SYN in brain tissues of these mice were studied with immunohistochemstry. The mean optical density （MOD） of immuno-stained SYN in the cerebral cortex, mossy fiber layer, hippocampus CA1, and cerebellar cortex were determined with an IBAS 2.0 image processor. Difference in MODs of SYN at these regions was examined using statistical software SPSS11.0 and compared among the groups. Results： By genotype, the expression of SYN was obviously decreased in all brain regions of KO mice compared with WT ones （P〈0.01） except in the mossy fiber layer, where significantly enhanced SYN expression was found in neonatal KO mice but not in the WT mice （P〈0.01）. By age, KO61W group showed higher level of SYN at all brain regions than KO^6W group, with more SYN in cerebral cortex （P〈0.01） and mossy fiber layer （P〈0.05） than in CA1. WT^1W mice showed more SYN in cerebral cortex and CA1 （P〈0.01）, and less SYN in mossy fiber （P〈0.01） as compared with WT^6W mice. Conclusion： Fewer synapses in the cerebral cortex and abnormally increased number of synapses in mossy fiber layer as found for FMRl-knockout mice may be parallel with mental retardation and increased neural excitability in patients with fragile X syndrome.