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Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice
Hongsheng Zhang,Eunchai Kang,Yaqing Wang,Chaojuan Yang,Hui Yu,Qin Wang,Zheyu Chen,Chen Zhang,Kimberly M. Christian,Hongjun Song,Guo-li Ming & Zhiheng Xu
NATURE COMMUNICATIONS
Abstract
Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specificCrmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown ofcrmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.
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论文编号: |
DOI:10.1038/ncomms11773 |
论文题目: |
Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice |
英文论文题目: |
Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice |
第一作者: |
Hongsheng Zhang,Eunchai Kang,Yaqing Wang,Chaojuan Yang,Hui Yu,Qin Wang,Zheyu Chen,Chen Zhang,Kimberly M. Christian,Hongjun Song,Guo-li Ming & Zhiheng Xu |
英文第一作者: |
Hongsheng Zhang,Eunchai Kang,Yaqing Wang,Chaojuan Yang,Hui Yu,Qin Wang,Zheyu Chen,Chen Zhang,Kimberly M. Christian,Hongjun Song,Guo-li Ming & Zhiheng Xu |
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2016-06-09 |
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Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specificCrmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown ofcrmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice. |
英文摘要: |
Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specificCrmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown ofcrmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice. |
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NATURE COMMUNICATIONS |
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NATURE COMMUNICATIONS |
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Hongsheng Zhang,Eunchai Kang,Yaqing Wang,Chaojuan Yang,Hui Yu,Qin Wang,Zheyu Chen,Chen Zhang,Kimberly M. Christian,Hongjun Song,Guo-li Ming & Zhiheng Xu. Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice. NATURE COMMUNICATIONS. DOI:10.1038/ncomms11773 |
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