Mice lacking the chromodomain helicase DNA-binding 5 chromatin remodeler display autism-like characteristics

M. T. Pisansky, A. E. Young, M. B. O'Connor, I. I. Gottesman, A. Bagchi, J. C. Gewirtz

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs. RNA sequencing of Chd5-/- mouse forebrain tissue revealed a preponderance of changes in expression of genes important in cellular development and signaling, sociocommunicative behavior and ASDs. Pyramidal neurons cultured from Chd5-/- cortex displayed alterations in dendritic morphology. Paralleling ASD nosology, Chd5-/- mice exhibited abnormal sociocommunicative behavior and a strong preference for familiarity. Chd5-/- mice further showed deficits in responding to the distress of a conspecific, a mouse homolog of empathy. Thus, dysregulated chromatin remodeling produces a pattern of transcriptional, neuronal and behavioral effects consistent with the presentation of ASDs.

Original languageEnglish (US)
Pages (from-to)e1152
JournalTranslational psychiatry
Issue number6
StatePublished - Jun 13 2017

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