Gantois Ilse, Vandesompele Jo, Speleman Frank, Reyniers Edwin, D'Hooge Rudi, Severijnen Lies-Anne, Willemsen Rob, Tassone Flora, Kooy R Frank
Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Neurobiol Dis. 2006 Feb;21(2):346-57. doi: 10.1016/j.nbd.2005.07.017. Epub 2005 Sep 30.
It is still unclear why absence of the fragile X protein (FMRP) leads to mental retardation and specific behavioral problems. In neurons, the protein transports specific mRNAs towards the actively translating ribosomes near the synapses. To unravel the mechanism leading to the disorder, we performed global gene expression analysis by means of the differential display method using the fragile X mouse model. To verify differential expression, we used microarray technology and real-time PCR. Three differentially expressed cDNAs showed consistent underexpression in the fragile X knockout mouse, including a GABA(A) receptor subunit delta, a Rho guanine exchange factor 12 and an EST BU563433. In addition, we identified 5 genes that showed differential expression dependent on the sample of RNA analysis. We consider their differential expression as provisional. It is possible that these differentially expressed genes play an important role in the cognitive and behavioral problems observed in the fragile X syndrome.
目前仍不清楚为何脆性X蛋白（FMRP）的缺失会导致智力迟钝和特定行为问题。在神经元中，该蛋白将特定的信使核糖核酸（mRNA）转运至突触附近正在积极进行翻译的核糖体处。为了阐明导致该病症的机制，我们借助差异显示法，利用脆性X小鼠模型进行了全基因组表达分析。为了验证差异表达，我们使用了微阵列技术和实时聚合酶链反应（PCR）。三个差异表达的互补脱氧核糖核酸（cDNA）在脆性X基因敲除小鼠中呈现出一致的低表达，包括一个γ-氨基丁酸A（GABA(A)）受体δ亚基、一个Rho鸟嘌呤核苷酸交换因子12和一个EST BU563433。此外，我们鉴定出5个基因，其表达差异取决于RNA分析的样本。我们认为它们的差异表达是暂时的。这些差异表达的基因有可能在脆性X综合征所观察到的认知和行为问题中发挥重要作用。
