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

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.

• Publication year

  2017

• Venue

  Translational Psychiatry

• Publication date

  2017-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/tp.2017.111PMID 28608855PMCID 5537637
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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