Transcriptomic profiling of zebrafish znf804a mutant heads under light cycling and dark only conditions

ABSTRACT: Sleep disturbances are a common symptom in individuals with schizophrenia and can exacerbate disruptions in cognitive processes like learning and memory. Elucidating pharmacologically targetable molecular pathways perturbed by high-risk schizophrenia genes may improve treatment outcomes. Here, we investigate the relationship between the schizophrenia gene znf804a and sleep and circadian behaviors/pathways. Using multi-day tracking of behavior, we show znf804a mutants display changes in circadian behaviors when external light cues are removed. Using bulk RNA sequencing of fish raised in normal light/dark and dark/dark conditions, we identified altered expression of genes in the core and auxiliary pathways controlling circadian rhythms. Further analysis revealed a znf804a-gene-dosage-dependent reduction in fbxl3a RNA expression. Transcriptomic analysis also revealed shifts in the relative abundance of specific transcripts without changing overall gene expression in genes linked to sleep and circadian pathways, including idh1, suggesting znf804a could influence transcript processing or stability. Together, these findings are the first to link ZNF804A orthologs to sleep and circadian phenotypes in model organisms and identify the regulation of fbxl3a and transcript processing as candidate mechanisms through which this schizophrenia risk gene may influence circadian biology.

ORGANISM(S): Danio rerio

PROVIDER: GSE328219 | GEO | 2026/07/31

REPOSITORIES: GEO