Paper - Review

DOI: 10.1038/tp.2017.111

Abstract

❗: ASD → shared a core set of nosological features
❓: ASD → exhibit substantial genetic heterogeneity

⁉: A parsimonious hypothesis
→ Dysregulated epigenetic mechanisms
→ represent common pathways ← in the etiology of ASDs

∴ Generated a novel mouse model
← resulting from brain-specific depletion of chromodomain helicase DNA-binding 5 (Chd5)
→ a chromatin remodeling protein
→ 1⃣ known to regulate neuronal differentiation 2⃣ 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 1⃣ cellular development 2⃣ signaling 3⃣ sociocommunicative behavior 4⃣ ASDs

Pyramidal neurons
← cultured from Chd5-/- cortex
→ displayed alterations ← in dendritic morphology

Chd5-/- mice
→ exhibited → 1⃣ abnormal sociocommunicative behavior 2⃣ a strong preference → for familiarity

Chd5-/- mice
→ showed deficits ← in responding to the distress
← of 1⃣ a conspecific 2⃣ a mouse homolog of empathy

∴ Dysregulated chromatic remodeling
→ produces → a pattern of 1⃣ transcriptional 2⃣ neuronal 3⃣ behavioral effects
← consistent with the presentation of ASDs

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