title: Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome.
abstract: A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizophrenia. To assess the models usefulness for drug discovery, a novel mouse (Df(h22q11)/+) was assessed in an extensive battery of cognitive assays by partners within the NEWMEDS collaboration (Innovative Medicines Initiative Grant Agreement No. 115008). This battery included classic and touchscreen-based paradigms with recognized sensitivity and multiple attempts at reproducing previously published findings in 22q11.2DS mouse models. This work represents one of the most comprehensive reports of cognitive functioning in a transgenic animal model. In accordance with previous reports, there were non-significant trends or marginal impairment in some tasks. However, the Df(h22q11)/+ mouse did not show comprehensive deficits; no robust impairment was observed following more than 17 experiments and 14 behavioral paradigms. Thus - within the current protocols - the 22q11.2DS mouse model fails to mimic the cognitive alterations observed in human 22q11.2 deletion carriers. We suggest that the 22q11.2DS model may induce liability for cognitive dysfunction with additional "hits" being required for phenotypic expression.
authors: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK Department of Psychology, State University of New York at Binghamton, Binghamton, NY 13902-6000, USA.
authors: Simon Ro
authors: SR
authors: Nilsson
authors: H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Ottiliavej 9, Valby 2500, Denmark.
authors: Kim
authors: K
authors: Fejgin
authors: In Vivo Pharmacology, Lilly Research Laboratories, Eli Lilly & Co. Ltd, Erl Wood Manor, Sunninghill Road, Windlesham GU20 6PH, UK.
authors: Francois
authors: F
authors: Gastambide
authors: Central Institute of Mental Health, Mannheim Faculty, University of Heidelberg, J5, 68159 Mannheim, Germany.
authors: Miriam A
authors: MA
authors: Vogt
authors: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors: Brianne A
authors: BA
authors: Kent
authors: H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Ottiliavej 9, Valby 2500, Denmark.
authors: Vibeke
authors: V
authors: Nielsen
authors: H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Ottiliavej 9, Valby 2500, Denmark.
authors: Jacob
authors: J
authors: Nielsen
authors: Central Institute of Mental Health, Mannheim Faculty, University of Heidelberg, J5, 68159 Mannheim, Germany.
authors: Peter
authors: P
authors: Gass
authors: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors: Trevor W
authors: TW
authors: Robbins
authors: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors: Lisa M
authors: LM
authors: Saksida
authors: H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Ottiliavej 9, Valby 2500, Denmark.
authors: Tine B
authors: TB
authors: Stensbøl
authors: In Vivo Pharmacology, Lilly Research Laboratories, Eli Lilly & Co. Ltd, Erl Wood Manor, Sunninghill Road, Windlesham GU20 6PH, UK.
authors: Mark D
authors: MD
authors: Tricklebank
authors: H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Ottiliavej 9, Valby 2500, Denmark.
authors: Michael
authors: M
authors: Didriksen
authors: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors: Timothy J
authors: TJ
authors: Bussey
mesh_terms: D000818:Animals; D001288:Attention; D003071:Cognition; D015331:Cohort Studies; D004062:DiGeorge Syndrome / Q000523:psychology*; D004192:Discrimination, Psychological; D004195:Disease Models, Animal; D055808:Drug Discovery; D056344:Executive Function; D005260:Female; D007266:Inhibition, Psychological; D007858:Learning; D008297:Male; D008568:Memory; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D010641:Phenotype; D057170:Translational Research, Biomedical
keywords: 22q11.2 deletion syndrome; animal model; cognition; copy number variation