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Elife. 2019 Apr 11;8. pii: e42819. doi: 10.7554/eLife.42819.

Shank3 modulates sleep and expression of circadian transcription factors.

Author information

1
Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, United States.
2
Istituto per le Applicazioni del Calcolo "M. Picone", Consiglio Nazionale della Ricerche, Napoli, Italy.
3
Dipartimento di Scienze Aziendali Management & Innovation Systems, University of Fusciano, Fisciano, Italy.
4
Department of Statistical Sciences, University of Padova, Padova, Italy.
5
Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, United States.
#
Contributed equally

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 of sleep problems in ASD. 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 prefrontal cortex gene expression between mutants and wild types, downregulating circadian transcription factors Per3, Bhlhe41, Hlf, Tef, and Nr1d1. 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.

KEYWORDS:

Shank3; autism spectrum disorder; mouse; neuroscience; sleep

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