Developmental disruption to the cortical transcriptome and synaptosome in a model of SETD1A loss-of-function

We employed a multi-omics approach to study the effects of heterozygous Setd1a LoF on gene expression and synaptic composition in mouse cortex across five developmental timepoints from embryonic day 14 to postnatal day 70. Using RNA sequencing, we observed that Setd1a LoF resulted in the consistent downregulation of genes enriched for mitochondrial pathways. This effect extended to the synaptosome, in which we found age-specific disruption to both mitochondrial and synaptic proteins. Quantification of RNA and protein alterations in mouse frontal cortex after heterozygous Setd1a knockout, at multiple stages of development