Qin Mei, Kang Julia, Burlin Thomas V, Jiang Chunhui, Smith Carolyn Beebe
Laboratory of Cerebral Metabolism, National Institute of Mental Health, United States Public Health Service, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
J Neurosci. 2005 May 18;25(20):5087-95. doi: 10.1523/JNEUROSCI.0093-05.2005.
Methylation-induced transcriptional silencing of the fragile X mental retardation-1 (Fmr1) gene leads to absence of the gene product, fragile X mental retardation protein (FMRP), and consequently fragile X syndrome (FrX), an X-linked inherited form of mental retardation. Absence of FMRP in Fmr1 null mice imparts some characteristics of the FrX phenotype, but the precise role of FMRP in neuronal function remains unknown. FMRP is an RNA-binding protein that has been shown to suppress translation of certain mRNAs in vitro. We applied the quantitative autoradiographic L-[1-14C]leucine method to the in vivo determination of regional rates of cerebral protein synthesis (rCPS) in adult wild-type (WT) and Fmr1 null mice at 4 and 6 months of age. Our results show a substantial decrease in rCPS in all brain regions examined between the ages of 4 and 6 months in both WT and Fmr1 null mice. Superimposed on the age-dependent decline in rCPS, we demonstrate a regionally selective elevation in rCPS in Fmr1 null mice. Our results suggest that the process of synaptic pruning during young adulthood may be reflected in decreased rCPS. Our findings support the hypothesis that FMRP is a suppressor of translation in brain in vivo.
甲基化诱导的脆性X智力低下1（Fmr1）基因转录沉默导致该基因产物脆性X智力低下蛋白（FMRP）缺失，进而引发脆性X综合征（FrX），这是一种X连锁遗传性智力低下。Fmr1基因敲除小鼠中FMRP的缺失赋予了FrX表型的一些特征，但FMRP在神经元功能中的精确作用仍不清楚。FMRP是一种RNA结合蛋白，已被证明在体外可抑制某些mRNA的翻译。我们应用定量放射自显影L-[1-14C]亮氨酸法在体内测定4个月和6个月大的成年野生型（WT）和Fmr1基因敲除小鼠脑蛋白合成区域速率（rCPS）。我们的结果显示，在4至6个月龄之间，WT和Fmr1基因敲除小鼠的所有检测脑区中rCPS均大幅下降。在rCPS随年龄下降的基础上，我们证明Fmr1基因敲除小鼠的rCPS存在区域选择性升高。我们的结果表明，成年早期的突触修剪过程可能反映在rCPS的降低上。我们的发现支持FMRP在体内是脑内翻译抑制因子的假说。
