title: Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.
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-specific Crmp2 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 of crmp2 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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Eunchai
authors.initials: E
authors.lastname: Kang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Chaojuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Zheyu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Christian
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.|Parkinson's Disease Center, Beijing Institute for Brain Disorders, Beijing 100871, China.
authors.forename: Zhiheng
authors.identifier: 0000-0002-4809-2851
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D002552:Cerebral Ventricles / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D008124:Locomotion / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012920:Social Behavior Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000235:genetics / Q000473:pathology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C095114:collapsin response mediator protein-2