title: Heterozygous deletion of α-neurexin I or α-neurexin II results in behaviors relevant to autism and schizophrenia.
abstract: The neurexins are a family of presynaptic cell adhesion molecules. Human genetic studies have found heterozygous deletions affecting NRXN1 and NRXN2, encoding α-neurexin I (Nrxn1α) and α-neurexin II (Nrxn2α), in individuals with autism spectrum disorders and schizophrenia. However, the link between α-neurexin deficiency and the manifestation of psychiatric disorders remain unclear. To assess whether the heterozygous loss of neurexins results in behaviors relevant to autism or schizophrenia, we used mice with heterozygous (HET) deletion of Nrxn1α or Nrxn2α. We found that in a test of social approach, Nrxn1α HET mice show no social memory for familiar versus novel conspecifics. In a passive avoidance test, female Nrxn1α HET mice cross to the conditioned chamber sooner than female wild-type and Nrxn2α HET mice. Nrxn2α HET mice also express a lack of long-term object discrimination, indicating a deficit in cognition. The observed Nrxn1α and Nrxn2α genotypic effects were specific, as neither HET deletion had effects on a wide range of other behavioral measures, including several measures of anxiety. Our findings demonstrate that the heterozygous loss of α-neurexin I and α-neurexin II in mice leads to phenotypes relevant to autism and schizophrenia.
authors.affiliation: School of Biomedical Sciences, University of Leeds.
authors.forename: James
authors.initials: J
authors.lastname: Dachtler
authors.affiliation: School of Biomedical Sciences, University of Leeds.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Ivorra
authors.affiliation: School of Biomedical Sciences, University of Leeds.
authors.forename: Tessa E
authors.initials: TE
authors.lastname: Rowland
authors.affiliation: Department of Psychology, Durham University.
authors.forename: Colin
authors.initials: C
authors.lastname: Lever
authors.affiliation: Institute of Psychological Sciences, University of Leeds.
authors.forename: R John
authors.initials: RJ
authors.lastname: Rodgers
authors.affiliation: School of Biomedical Sciences, University of Leeds.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001321:Autistic Disorder; D002135:Calcium-Binding Proteins; D003071:Cognition / Q000502:physiology; D004192:Discrimination, Psychological / Q000502:physiology*; D005260:Female; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D012565:Schizophrenic Psychology; D017384:Sequence Deletion; D012919:Social Behavior
chemical_list: D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; C093175:neurexin II