GSE109328
Epigenetic Rescue of Autism-like Social Deficits in Shank3-Deficient Mouse Models
To determine whether histone deacetylase (HDAC) inhibition has genome-wide effects on gene expression, we used RNA sequencing to analyze the mRNA profile in prefrontal cortex (PFC) of wild-type (WT) and Shank3-deficient (Shank3+/?C) mice treated with romidespin or saline control. We mapped the sequences to 24,420 mouse genes. Compared to WT, 365 genes in saline-treated Shank3+/?C mice showed a change in expression values of at least 1.2 fold and p = 0.01 (213 downregulated, 152 upregulated). In romidepsin-treated Shank3+/?C mice, ~88% of the downregulated genes (n=187 genes) were normalized to control values. Further analysis of the romidepsin-restored genes revealed enrichment in actin cytoskeleton-mediated transport, signal transduction pathways, and developmental processes. Overall design: Comparison of gene expression in prefrontal cortex of wild-type mice, saline-treated Shank3-deficient mice and romidepsin-treated mice Heterozygous Shank3+/?C mice (5-8 weeks old, male) expressing C-terminal (exon 21) deleted Shank3 (Jackson Labs), which exhibited the significant loss of full-length Shank3 expression, and age-matched wild-type littermates (male), were used in the experiments.