Establishment of Common Marmoset Carrying a Frameshift Mutation in SETD1A, a Schizophrenia Risk Gene

To better understand the epigenetic and neurobiological consequences of SETD1A dysfunction, non-human primate models can serve as a useful tool because of their close evolutionary relationship to humans and highly developed cognitive abilities. In this study, we established a genetically engineered common marmoset (Callithrix jacchus) lineage carrying a frameshift mutation in SETD1A. In mutant marmoset cells, we confirmed a reduction in SETD1A protein expression which is accompanied by alterations in histone methylation patterns and global gene transcription, indicating broad epigenomic and transcriptional disruption.

These findings demonstrate that the substantial molecular and regulatory perturbations induced by SETD1A haploinsufficiency are also observed in marmosets, underscoring the evolutionary conserved function of SETD1A in mammals. Collectively, our SETD1A mutant marmosets provide a valuable platform for bridging molecular mechanisms with primate neurobiology and for investigating the role of epigenetic regulation in the pathophysiology of neuropsychiatric and neurodevelopmental disorders.