Fig. 5: NEXMIF restoration globally rescues the expression of dysregulated hippocampal genes associated with Nexmif loss.

A RNA sequencing heat map showing the normalized expression values of the top 125 differentially expressed genes (DEGs) in the hippocampus (HPC) of a WT + CTRL mouse (left column), a KO + CTRL mouse (middle column), and a KO + NEX mouse (right column). 78 DEGs (62%) were downregulated and 47 DEGs (38%) were upregulated in the KO + CTRL mouse brain relative to the WT + CTRL mouse brain. Of the 125 DEGs, 58 were restored in expression by greater than 70% in the KO + NEX mouse brain. B Gene Ontology (GO) analysis bar chart depicting the most enriched biological processes. The total percentage of each bar reflects the total number of DEGs from the dataset within each GO biological process. Each bar is partitioned by the percentage of downregulated (green) versus upregulated (red) DEGs in the KO + CTRL mouse brain relative to that of WT + CTRL. C Gene Ontology (GO) analysis bar chart indicating the percentage of “Rescued” versus “Not Rescued” DEGs. The total percentage of each bar reflects the total number of DEGs from the dataset within each GO biological process. Each bar is partitioned into the percentage of “Rescued” (red) versus “Not rescued” (gray) DEGs in the KO + NEX mouse brain relative to that of WT + CTRL. A “Rescued” DEG is defined as a gene whose expression was restored in the KO + NEX brain to within ± 30% of its WT + CTRL expression level. For example, Gene A has an expression level of 100 arbitrary units (AU) in the WT + CTRL condition. Gene A is downregulated to 15 AU in the KO + CTRL condition. In the KO + NEX condition, Gene A has an expression level of 90 AU. Gene A is considered as “rescued” because its expression level of 90 AU in the KO + NEX condition is within the ± 30% range (70–130) of Gene A’s basal expression level in the WT + CTRL condition.