Comprehensive behavioral study and proteomic analyses of CRMP 2‐deficient mice

Collapsin response mediator protein 2 ( CRMP 2) plays a key role in axon guidance, dendritic morphogenesis and cell polarization. CRMP 2 is implicated in various neurological and psychiatric disorders. However, in vivo functions of CRMP 2 remain unknown. We generated CRMP 2 gene‐deficient ( crmp2 −/− ) mice and examined their behavioral phenotypes. During 24‐h home cage monitoring, the activity level during the dark phase of crmp2 −/− mice was significantly higher than that of wild‐type ( WT ) mice. Moreover, the time during the open arm of an elevated plus maze was longer for crmp2 −/− mice than for WT mice. The duration of social interaction was shorter for crmp2 −/− mice than for WT mice. Crmp2 −/− mice also showed mild impaired contextual learning. We then examined the methamphetamine‐induced behavioral change of crmp2 −/− mice. Crmp2 −/− mice showed increased methamphetamine‐induced ambulatory activity and serotonin release. Crmp2 −/− mice also showed altered expression of proteins involved in GABA ergic synapse, glutamatergic synapse and neurotrophin signaling pathways. In addition, SNAP 25, RAB 18, FABP 5, ARF 5 and LDHA , which are related genes to schizophrenia and methamphetamine sensitization, are also decreased in crmp2 −/− mice. Our study implies that dysregulation of CRMP 2 may be involved in pathophysiology of neuropsychiatric disorders.