Two selected models of missense mutations in mice for the study of learning behaviour

A large number of genome-wide association studies have linked missense mutations, mutations altering the amino acid sequence of proteins, with cognitive impairment in humans. However, these studies are correlative. As there may be multiple mutations for one particular patient, it is essential to address the functional impact of a missense mutation in a model system. The most suitable model system is the generation of knock-in mice with the homologous missense mutation followed by behavioural phenotyping. Here, we review selected mutants demonstrating an impact of single mutations on learning and memory in mice and discuss the relevance of such studies for understanding the role of these polymorphisms in human behaviour. We conclude that using these animal models has been instrumental in decoding the mechanisms underlying behaviour, and assists the design of therapeutic strategies for humans.

► Impact of missense mutations can be studied in mice.
► In mice the αCaMKII-T286A mutation causes severe memory deficit.
► Analysis of BDNF-V66M mutation establishes its role in cognitive impairment.