Cavallaro Sebastiano, Paratore Sabrina, Fradale Francesco, de Vrij Femke M S, Willemsen Rob, Oostra Ben A
Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
Neurobiol Dis. 2008 Dec;32(3):510-20. doi: 10.1016/j.nbd.2008.09.008. Epub 2008 Sep 30.
Fragile X syndrome is a common inherited form of mental retardation and originates from the absence of expression of the FMR1 gene. This gene and its two homologues, FXR1 and FXR2, encode for a family of fragile X related (FXR) proteins with similar tissue distribution, together with sequence and functional homology. Based on these characteristics, it has been suggested that these proteins might partly complement one another. To unravel the function of Fxr2 protein, the expression pattern of 12,588 genes was studied in the brains of wild-type and Fxr2 knockout mice, an animal model which shows behavioral abnormalities partly similar to those observed in Fmr1-knockout mice. By genome expression profiling and stringent significance tests we identify genes and gene groups de-regulated in the brains of Fxr2 knockout mice. Differential expression of candidate genes was validated by real-time PCR, in situ hybridization, immunohistochemistry and western blot analysis. A number of differentially expressed genes associated with the Fxr2 phenotype have been previously involved in other memory or cognitive disorders.
脆性X综合征是一种常见的遗传性智力障碍形式，由FMR1基因表达缺失引起。该基因及其两个同源基因FXR1和FXR2编码一组脆性X相关（FXR）蛋白，它们具有相似的组织分布以及序列和功能同源性。基于这些特征，有人提出这些蛋白可能部分相互补充。为了阐明Fxr2蛋白的功能，研究了野生型和Fxr2基因敲除小鼠大脑中12588个基因的表达模式，该动物模型表现出的行为异常部分类似于Fmr1基因敲除小鼠中观察到的异常。通过基因组表达谱分析和严格的显著性检验，我们鉴定出在Fxr2基因敲除小鼠大脑中失调的基因和基因组。候选基因的差异表达通过实时PCR、原位杂交、免疫组织化学和蛋白质印迹分析进行验证。许多与Fxr2表型相关的差异表达基因先前已涉及其他记忆或认知障碍。
