GSE168211
Dosage-dependent differential transcriptomic changes in the prefrontal cortex of heterozygous and homozygous Shank2-mutant mice
Shank2 is an abundant postsynaptic scaffolding protein known to regulate excitatory synaptic assembly and function and is implicated in autism spectrum disorders (ASD). Whereas patient Shank2 mutations in autistic individuals are heterozygous, Shank2 functions studied in mice have mainly relied on the results from homozygous mutant mice, largely because of relatively strong synaptic and behavioral phenotypes. Moreover, although synaptic changes at juvenile and adult Shank2-mutant mice seem to be largely similar, it remains unclear whether there are any age-dependent changes across these stages at the molecular level. To address these questions, we attempted RNA-Seq analyses of the transcriptomes in the prefrontal cortex of both heterozygous and homozygous Shank2-mutant mice lacking exons 6 and 7 at juvenile and adult stages. The results indicate that heterozygous, but not homozygous, juvenile Shank2-mutant mice show strong transcriptomic changes that promote excitatory synaptic transmission and suppress ASD-related gene expressions. In contrast, adult Shank2-mutant mice show largely similar and dosage-dependent transcriptomic changes. Overall design: Transcriptome analysis of Shank2 heterozygote and homozygous mutant and wild-type mice at ages of 3 week and 12 week