Correction of fragile X syndrome in mice

被引:734
作者
Dolen, Gul [1 ,2 ,3 ]
Osterweil, Emily [1 ]
Rao, B. S. Shankaranarayana [4 ]
Smith, Gordon B. [1 ]
Auerbach, Benjamin D. [1 ]
Chattarji, Sumantra [5 ]
Bear, Mark F. [1 ]
机构
[1] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Howard Hughes Med Inst, Cambridge, MA 02139 USA
[2] Brown Univ, Sch Med, Dept Neurosci, Providence, RI 02912 USA
[3] Div Biol & Med, Providence, RI 02912 USA
[4] Natl Inst Mental Hlth & Neurosci, Dept Neurophysiol, Bangalore 560002, Karnataka, India
[5] Tata Inst Fundamental Res, Natl Ctr Biol Sci, Bangalore 560002, Karnataka, India
关键词
D O I
10.1016/j.neuron.2007.12.001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:955 / 962
页数:8
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