The bipolar disorder GWAS risk gene NEK4 modulates circadian fluctuations of murine emotional behaviors and synaptogenesis

ABSTRACT: Through integrative analyses of GWAS summary statistics, population genetic data and expression quantitative trait loci (eQTL) annotations, we found that elevated NEK4 expression in hippocampus was causatively linked to the risk of BD. To examine the biological impact of this gene, we generated NEK4 conditional knock-in mice in pyramidal neurons of the adult forebrain (NEK4 cKI mice) and NEK4 overexpression mice with adeno-associated virus (AAV) mediated in the dorsal hippocampus (NEK4 OE mice). Since NEK4 encodes a serine/threonine kinase, we explored the phosphoproteomic profiles of these mice at different time of the day and compared them with those of the control mice. We isolated the hippocampal proteins of the NEK4 OE mice and the control mice during day and night respectively (n = 3 for each group), and performed phosphorylated 4D-label-free quantitative proteomics analyses. After stringent quality control, 5376 quantifiable phosphorylated peptides were identified in 2415 phosphorylated proteins

ORGANISM(S): Mus <genus>

SUBMITTER: Ming Li  

PROVIDER: PXD052190 | iProX | Sat May 11 00:00:00 GMT+01:00 2024

REPOSITORIES: iProX