摘要：SummaryRecent clinical studies report that chromosomal 12q24.31 microdeletions are associated with autism spectrum disorder (ASD) and intellectual disability (ID). However, the causality and underlying mechanisms linking 12q24.31 microdeletions to ASD/ID remain undetermined. Here we showKdm2b, one gene located in chromosomal 12q24.31, plays a critical role in maintaining neural stem cells (NSCs) in the mouse brain. Loss of the CxxC-ZF domain of KDM2B impairs its function in recruiting Polycomb repressive complex 1 (PRC1) to chromatin, resulting in de-repression of genes involved in cell apoptosis, cell-cycle arrest, NSC senescence, and loss of NSC populations in the brain. Of importance, theKdm2bmutation is sufficient to induce ASD/ID-like behavioral and memory deficits. Thus, our study reveals a critical role of KDM2B in normal brain development, a causality between theKdm2bmutation and ASD/ID-like phenotypes in mice, and potential molecular mechanisms linking the function of KDM2B-PRC1 in transcriptional regulation to the 12q24.31 microdeletion-associated ASD/ID.Graphical abstractDisplay OmittedHighlights•Kdm2bmutation impairs neural stem cell self-renewal•Kdm2bmutation causes autistic-like behaviors and memory deficits•Kdm2bmutation derepresses genes related to impaired NSC self-renewal•Kdm2bmutation impairs PRC1 recruitment to chromatinBiological sciences; Molecular biology; Neuroscience
