Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome

Cereb Cortex. 2016 Oct;26(10):3991-4003. doi: 10.1093/cercor/bhw229. Epub 2016 Aug 9.


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.

Keywords: 22q11.2 deletion syndrome; animal model; cognition; copy number variation.

MeSH terms

  • Animals
  • Attention
  • Cognition*
  • Cohort Studies
  • DiGeorge Syndrome / psychology*
  • Discrimination, Psychological
  • Disease Models, Animal*
  • Drug Discovery
  • Executive Function
  • Female
  • Inhibition, Psychological
  • Learning
  • Male
  • Memory
  • Mice, Inbred C57BL
  • Mice, Transgenic*
  • Neuropsychological Tests
  • Phenotype
  • Translational Research, Biomedical