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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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CA1 Region, Hippocampal / growth & development
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CA1 Region, Hippocampal / metabolism*
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CA1 Region, Hippocampal / pathology
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Cerebral Ventricles / growth & development
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Cerebral Ventricles / metabolism
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Cerebral Ventricles / pathology
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Disease Models, Animal
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Gene Expression Regulation, Developmental
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Intercellular Signaling Peptides and Proteins / deficiency*
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Intercellular Signaling Peptides and Proteins / genetics
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Locomotion / genetics
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Long-Term Potentiation / genetics
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Male
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Maze Learning
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Memory Disorders / genetics*
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Memory Disorders / metabolism
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Memory Disorders / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nerve Tissue Proteins / deficiency*
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Nerve Tissue Proteins / genetics
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Neurogenesis / genetics*
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Neuronal Plasticity / genetics
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Neurons / metabolism*
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Neurons / pathology
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Receptors, N-Methyl-D-Aspartate / genetics
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Receptors, N-Methyl-D-Aspartate / metabolism
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Schizophrenia / genetics*
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Schizophrenia / metabolism
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Schizophrenia / pathology
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Social Behavior Disorders / genetics*
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Social Behavior Disorders / metabolism
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Social Behavior Disorders / pathology
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Synapses / genetics
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Synapses / pathology
Substances
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Intercellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Receptors, N-Methyl-D-Aspartate
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collapsin response mediator protein-2