Mouse models of genetic effects on cognition: relevance to schizophrenia.

Abstract

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.

• Authors: Francesco Papaleo, Barbara K Lipska, Daniel R Weinberger
• Journal: Neuropharmacology (Neuropharmacology) Vol. 62 Issue 3 Pg. 1204-20 (Mar 2012) ISSN: 1873-7064 [Electronic] England
• PMID: 21557953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011. Published by Elsevier Ltd.

Topics

• Animals
• Cognition
• Cognition Disorders (genetics, psychology)
• Disease Models, Animal
• Humans
• Mice
• Reelin Protein
• Schizophrenia (genetics)
• Schizophrenic Psychology
• Species Specificity