title: Missense mutation of the reticulon-4 receptor alters spatial memory and social interaction in mice.
abstract: The reticulon-4 receptor, encoded by RTN4R, limits axonal sprouting and neural plasticity by inhibiting the outgrowth of neurites. Human association studies have implicated mutations in RTN4R in the development of schizophrenia, including the identification of several rare nonconservative missense mutations of RTN4R in schizophrenia patients. To investigate the effects of missense mutation of the reticulon-4 receptor on phenotypes relevant to schizophrenia, we behaviourally characterized a novel Rtn4r mutant mouse line with an amino acid substitution (R189H) in the Nogo-66 binding site. Behavioural assays included prepulse inhibition of acoustic startle, locomotor activity, social interaction and spatial cognition. When compared with wildtype littermates, Rtn4r mutant mice exhibited greater social preference, which may reflect a social-anxyolitic effect, and a mild impairment in spatial cognition. Given the mild effect of the R189H mutation of Rtn4r on behavioural phenotypes relevant to schizophrenia, our results do not support missense mutation of RTN4R as a strong risk factor in the pathogenesis of schizophrenia.
authors.affiliation: Department of Psychology, University of Western Ontario, London, ON, Canada. nlazar@uwo.ca
authors.forename: Noah L
authors.initials: NL
authors.lastname: Lazar
authors.forename: Shiva
authors.initials: S
authors.lastname: Singh
authors.forename: Tara
authors.initials: T
authors.lastname: Paton
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Gondo
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Fukumura
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.forename: Donald P
authors.initials: DP
authors.lastname: Cain
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001120:Arginine / Q000235:genetics; D001522:Behavior, Animal; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000235:genetics; D006639:Histidine / Q000235:genetics; D007266:Inhibition, Psychological; D007398:Interpersonal Relations; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics*; D009185:Myelin Proteins / Q000172:deficiency / Q000235:genetics*; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics*; D012022:Reflex, Acoustic / Q000235:genetics
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C486581:Rtn4r protein, rat; D006639:Histidine; D001120:Arginine