| First Author | Pisansky MT | Year | 2017 |
| Journal | Transl Psychiatry | Volume | 7 |
| Issue | 6 | Pages | e1152 |
| PubMed ID | 28608855 | Mgi Jnum | J:255416 |
| Mgi Id | MGI:6114454 | Doi | 10.1038/tp.2017.111 |
| Citation | Pisansky MT, et al. (2017) Mice lacking the chromodomain helicase DNA-binding 5 chromatin remodeler display autism-like characteristics. Transl Psychiatry 7(6):e1152 |
| abstractText | 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. |
