Temporal analysis of blood transcriptome in a circadian-disrupted macaque model

Circadian dysfunction has been recognized as a risk factor for metabolic, psychiatric and age-related disorders. In the study we generated a macaque monkey model with circadian disruption to investigate circadian-related human symptoms. By ablating BMAL1 with CRISPR/Cas9 editing in cynomolgus monkeys, we obtained monkeys showing higher nocturnal activities and depression phenotypes. BMAL1 ablation up-regulated transcriptional programs toward inflammatory and stress responses, and transcription network analysis showed significant correlation with those associated with human sleep deprivation, major depressive disorder, and aging. Thus, the model offers opportunities for studying physiological consequences of circadian disturbance, and for developing interventions for circadian-related psychiatric and chronic diseases.