| Experiment Id | GSE178844 | Name | p53-mediated neurodegeneration in the absence of the nuclear protein Akirin2 |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-02-24 |
| description | Purpose: We investigated the molecular function of the nuclear protein, Akirin2 (Aki2), in postmitotic excitatory cortical neurons and neural progenitor cells of the embryonic dorsal telencephalon. Method: We performed total RNA-Sequencing on the cortex of P35 CaMK-Cre;Aki2fl/fl mice and age matched controls. We compared this transcriptomic database to one obtained through total RNA-Sequencing of E10.5 Emx1-Cre;Aki2fl/fl dorsal telencephalon and age-matched controls . Results: We discovered slow degeneration through necroptosis in the Aki2 postmitotic forebrain mutants and dysregulation of many p53 target genes in both transcriptomics datasets. Reduction of the p53 gene in the CaMK-Cre;Aki2fl/fl line delays cell death; while knockout prevents it entirely. Conclusion: This study provides insight into the molecular mechanisms of Aki2 function in cortical neurons and identifies p53 as a molecular mediator of neuronal death in the absence of Aki2. Furthermore, it identifies several candidate Aki2-dependent genes dysregulated in both transcroptomic datasets and many candidate Aki2 target genes that are context dependent. Cortical mRNA profiles of three P35 CaMK-Cre;Ak2fl/fl and four littermate control mice; dorsal telencephalon mRNA profile of four E10.5 Emx1-Cre;Aki2fl/fl and four littermate controls |
