TY - JOUR
T1 - Mouse models of genetic effects on cognition
T2 - Relevance to schizophrenia
AU - Papaleo, Francesco
AU - Lipska, Barbara K.
AU - Weinberger, Daniel R.
N1 - Funding Information:
We thank Dr. J.N. Crawley, Dr. G. Carr and A. Bebensee for critical reading of the manuscript. Authors were supported by the Intramural Program of the NIH, NIMH, and the Italian Institute of Technology . FP was also supported by the Marie Curie FP7-Reintegration -Grant No 268247 . The authors declare that they have no financial conflict of interest.
PY - 2012/3
Y1 - 2012/3
N2 - 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'
AB - 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'
KW - Behavior
KW - Cognition
KW - Genes
KW - Mouse
KW - Schizophrenia
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U2 - 10.1016/j.neuropharm.2011.04.025
DO - 10.1016/j.neuropharm.2011.04.025
M3 - Review article
C2 - 21557953
AN - SCOPUS:84856100262
VL - 62
SP - 1204
EP - 1220
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 3
ER -