PR002379 (Project)

Description:Loss-of-function mutations in ZMYM2 are associated with an increased risk for schizophrenia (SCZ) and neurodevelopmental disorders (NDD). ZMYM2 interacts with proteins that regulate histone modifications and gene expression, but its functions in the brain are unclear. In this multi-omics study, we found that Zmym2 heterozygous knockout in mice leads to widespread disturbance of gene expression and alterations in diverse molecular pathways, including those related to histone modifications and neuronal activity, particularly in neurons. Proteomic analysis of synapses uncovered dysregulation in lipid metabolism and neurofilament pathways. In neurophysiologic and behavioral tests, Zmym2+/- mutant mice exhibit abnormal EEG patterns and locomotor activity. Our findings underscore the critical role of ZMYM2 in brain development and function and establish Zmym2 mutant mice as a useful genetically valid animal model for SCZ and NDD.