Mouse models of genetic effects on cognition: Relevance to schizophrenia

Francesco Papaleo, Barbara K. Lipska, Daniel R. Weinberger

Research output: Contribution to journalReview articlepeer-review

86 Scopus citations


Cognitive dysfunction is a core feature of schizophrenia. Growing evidence indicates that a wide variety of genetic mutations and polymorphisms impact cognition and may thus be implicated in various aspects of this mental disorder. Despite differences between human and rodent brain structure and function, genetic mouse models have contributed critical information about brain mechanisms involved in cognitive processes. Here, we summarize discoveries of genetic modifications in mice that impact cognition. Based on functional hypotheses, gene modifications within five model systems are described: 1) dopamine (D1, D2, D3, D4, D5, DAT, COMT, MAO); 2) glutamate (GluR-A, NR1, NR2A, NR2B, GRM2, GRM3, GLAST); 3) GABA (α 5, γ 2, α 4, δGABA A, GABA B(1), GAT1); 4) acetylcholine (nAChRβ2, α7, CHRM1); and 5) calcium (CaMKII-α, neurogranin, CaMKKβ, CaMKIV). We also consider other risk-associated genes for schizophrenia such as dysbindin (DTNBP1), neuregulin (NRG1), disrupted-in-schizophrenia1 (DISC1), reelin and proline dehydrogenase (PRODH). Because of the presumed importance of environmental factors, we further consider genetic modifications within the stress-sensitive systems of corticotropin-releasing factor (CRF), brain-derived neurotrophic factor (BDNF) and the endocannabinoid systems. We highlight the missing information and limitations of cognitive assays in genetically modified mice models relevant to schizophrenia pathology. This article is part of a Special Issue entitled 'Schizophrenia'

Original languageEnglish (US)
Pages (from-to)1204-1220
Number of pages17
Issue number3
StatePublished - Mar 2012
Externally publishedYes


  • Behavior
  • Cognition
  • Genes
  • Mouse
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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