小鼠中脆性X综合征的纠正。
Correction of fragile X syndrome in mice.
作者信息
Dölen Gül, Osterweil Emily, Rao B S Shankaranarayana, Smith Gordon B, Auerbach Benjamin D, Chattarji Sumantra, Bear Mark F
机构信息
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Neuron. 2007 Dec 20;56(6):955-62. doi: 10.1016/j.neuron.2007.12.001.
Abstract
Fragile X syndrome (FXS) is the most common form of heritable mental retardation and the leading identified cause of autism. FXS is caused by transcriptional silencing of the FMR1 gene that encodes the fragile X mental retardation protein (FMRP), but the pathogenesis of the disease is unknown. According to one proposal, many psychiatric and neurological symptoms of FXS result from unchecked activation of mGluR5, a metabotropic glutamate receptor. To test this idea we generated Fmr1 mutant mice with a 50% reduction in mGluR5 expression and studied a range of phenotypes with relevance to the human disorder. Our results demonstrate that mGluR5 contributes significantly to the pathogenesis of the disease, a finding that has significant therapeutic implications for fragile X and related developmental disorders.
摘要
脆性X综合征（FXS）是遗传性智力障碍最常见的形式，也是已确定的自闭症的主要病因。FXS是由编码脆性X智力障碍蛋白（FMRP）的FMR1基因转录沉默引起的，但该疾病的发病机制尚不清楚。根据一种观点，FXS的许多精神和神经症状是由代谢型谷氨酸受体mGluR5的不受控制的激活导致的。为了验证这一观点，我们培育了mGluR5表达降低50%的Fmr1突变小鼠，并研究了一系列与人类疾病相关的表型。我们的结果表明，mGluR5对该疾病的发病机制有显著贡献，这一发现对脆性X及相关发育障碍具有重要的治疗意义。
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