title: Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline.
abstract: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear.
  
  
  
  In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment.
  
  
  
  Attentional function in mice haploinsufficient for Map2k7 (Map2k7+/-mice) was investigated using the five-choice serial reaction time task (5-CSRTT).
  
  
  
  Once stable performance had been achieved, Map2k7+/-mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline-a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia-signs of improvement in attentional performance were detected.
  
  
  
  Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline.
authors: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow, G12 8QQ, UK.
authors: R L
authors: RL
authors: Openshaw
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.
authors: D M
authors: DM
authors: Thomson
authors: Institute for Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030, Vienna, Austria.
authors: J M
authors: JM
authors: Penninger
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.
authors: J A
authors: JA
authors: Pratt
authors: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow, G12 8QQ, UK. Brian.Morris@glasgow.ac.uk.
authors: B J
authors: BJ
authors: Morris
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D005260:Female; D057895:Haploinsufficiency / Q000235:genetics*; D006801:Humans; D048688:MAP Kinase Kinase 7 / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*
chemical_list: D048688:MAP Kinase Kinase 7; C482570:Map2k7 protein, mouse; D008911:Minocycline
keywords: Attention; Cognition; JNK; MAP kinase; MKK7