Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

Abstract

AbstractSeveral genome- and proteome-wide studies have associated transcription and translation changes ofCRMP2(collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brainin vivo. Here we show that brain-specificCrmp2knockout (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 ofCrmp2in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown ofcrmp2specifically 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.