Academic Commons

Articles

Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice.

Courchet, Virginie; Roberts, Amanda J.; Meyer-Dilhet, GĂ©raldine; Del Carmine, Peggy; Lewis, Jr., Tommy Len; Polleux, Franck; Courchet, Julien

Recently, numerous rare de novo mutations have been identified in patients diagnosed with autism spectrum disorders (ASD). However, despite the predicted loss-of-function nature of some of these de novo mutations, the affected individuals are heterozygous carriers, which would suggest that most of these candidate genes are haploinsufficient and/or lead to expression of dominant-negative forms of the protein. Here, we tested this hypothesis with the candidate ASD gene Nuak1 that we previously identified for its role in the development of cortical connectivity. We report that Nuak1 is haploinsufficient in mice with regard to its function in cortical development. Furthermore Nuak1+/- mice show a combination of abnormal behavioral traits ranging from defective spatial memory consolidation, defects in social novelty (but not social preference) and abnormal sensorimotor gating. Overall, our results demonstrate that Nuak1 haploinsufficiency leads to defects in the development of cortical connectivity and a complex array of behavorial deficits.

Files

  • thumnail for Courchet_et_al-2018-Nature_Communications.pdf Courchet_et_al-2018-Nature_Communications.pdf application/pdf 7.35 MB Download File

Also Published In

Title
Nature Communications
DOI
https://doi.org/10.1038/s41467-018-06584-5

More About This Work

Academic Units
Neuroscience
Published Here
November 8, 2018