Nov 8, 2018

Shank3 Modulates Sleep and Expression of Circadian Transcription Factors

BioRxiv : the Preprint Server for Biology
Ashley IngiosiLucia Peixoto

Abstract

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. We investigated the role of Shank3 , a high confidence ASD gene candidate, in sleep architecture and regulation. We show that mice lacking exon 21 of Shank3 have problems falling asleep even when sleepy. Using RNA-seq we show that sleep deprivation increases the differences in gene expression between mutants and wild types, downregulating circadian transcription factors Per3 , Dec2 , Hlf , Tef , and Reverbα . Shank3 mutants also have trouble regulating wheel-running activity in constant darkness. Overall our study shows that Shank3 is an important modulator of sleep and clock gene expression.

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Mentioned in this Paper

BHLHE41
Study
Shank3
BHLHE41 gene
Exons
Per3
Regulation of Biological Process
Sequence Determinations, RNA
SH3 and Multiple Ankyrin Repeat Domains Protein 3
SHANK3 gene

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