title: Reduced expression of STOP/MAP6 in mice leads to cognitive deficits.
abstract: BACKGROUND
  STOP/MAP6 null (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6 proteins in heterozygous mice (only one allele expressed) would result in abnormal behavior related to those displayed by STOP null mice.
  
  
  METHODS
  Using a comprehensive test battery, we investigated the behavioral phenotype of STOP heterozygous (Het) mice compared with STOP KO and wild type (WT) mice on animals raised either in standard conditions (controls) or submitted to maternal deprivation.
  
  
  RESULTS
  Control Het mice displayed prominent deficits in social interaction and learning, resembling KO mice. In contrast, they exhibited short-lasting locomotor hyperreactivity to acute mild stress and no impaired locomotor response to amphetamine, much like WT mice. Additionally, perinatal stress deteriorated Het mouse phenotype by exacerbating alterations related to positive symptoms such as their locomotor reactivity to acute mild stress and psychostimulant challenge.
  
  
  CONCLUSIONS
  Results show that the dosage of susceptibility genes modulates their putative phenotypic contribution and that STOP expression has a high penetrance on cognitive abilities. Hence, STOP Het mice might be useful to investigate cognitive defects related to those observed in mental diseases and ultimately might be a valuable experimental model to evaluate preventive treatments.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Volle
authors.forename: Jacques
authors.initials: J
authors.lastname: Brocard
authors.forename: Mohamed
authors.initials: M
authors.lastname: Saoud
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gory-Faure
authors.forename: Jérôme
authors.initials: J
authors.lastname: Brunelin
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Suaud-Chagny
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D059647:Gene-Environment Interaction; D006579:Heterozygote; D008124:Locomotion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D010641:Phenotype; D012559:Schizophrenia / Q000209:etiology* / Q000235:genetics
chemical_list: D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse