Mouse models of genetic effects on cognition:... : Neuropharmacology (original) (raw)

Mouse models of genetic effects on cognition: Relevance to schizophrenia

Francesco Papaleo
Barbara K. Lipska
Daniel R. Weinberger

Neuropharmacology

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1204

1220

March 2012

| DOI: 10.1016/j.neuropharm.2011.04.025

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 (α5, γ2, α4, δGABAA, GABAB(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’

Highlights

▸ Genetic mutations in mice relevant to schizophrenia that impact cognition. ▸ Mouse models contributed critical information about cognitive processes. ▸ Important to understand the causes and developing of treatment for schizophrenia. ▸ A guide to genetic modifications and derived cognitive consequences. ▸ We provide the advantages, missing information and limitations.