Shank3 Modulates Sleep and Expression of Circadian Transcription Factors

Autism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States and often co-presents with sleep problems. Sleep problems in ASD predict the severity of ASD core diagnostic symptoms and have a considerable impact on the quality of life of caregivers. Little is known, however, about the underlying molecular mechanisms of sleep problems in ASD. We investigated the role ofShank3, a high confidence ASD gene candidate, in sleep architecture and regulation. We show that mice lacking exon 21 ofShank3 have problems falling asleep even when sleepy. Using RNA-seq we show that sleep deprivation increases the differences in prefrontal cortex gene expression between mutants and wild types, downregulating circadian transcription factorsPer3,Bhlhe41,Hlf,Tef, andNr1d1. Shank3 mutants also have trouble regulating wheel-running activity in constant darkness. Overall, our study shows thatShank3 is an important modulator of sleep and clock gene expression.
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research