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Shank3 Modulates Sleep and Expression of Circadian Transcription Factors

Ashley M. Ingiosi, Taylor Wintler, Hannah Schoch, Kristan G. Singletary, View ORCID ProfileDario Righelli, Leandro G. Roser, Davide Risso, Marcos G. Frank, View ORCID ProfileLucia Peixoto
doi: https://doi.org/10.1101/465799
Ashley M. Ingiosi
1Department of Biomedical Science, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, United States
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Taylor Wintler
1Department of Biomedical Science, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, United States
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Hannah Schoch
1Department of Biomedical Science, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, United States
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Kristan G. Singletary
1Department of Biomedical Science, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, United States
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Dario Righelli
2Instituto per le Applicazioni del Calcolo “M. Picone”, Consiglio Nazionale della Ricerche, Napoli, Italy. Dipartimento di Scienze Aziendali Management & Innovative Systems, Università di Fisciano, Fisciano, Italy.
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Leandro G. Roser
1Department of Biomedical Science, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, United States
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Davide Risso
3Department of Statistical Sciences, University of Padova, Padova, Italy and Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, New York, United States
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Marcos G. Frank
1Department of Biomedical Science, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, United States
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  • For correspondence: lucia.peixoto@wsu.edu marcos.frank@wsu.edu
Lucia Peixoto
1Department of Biomedical Science, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, United States
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  • ORCID record for Lucia Peixoto
  • For correspondence: lucia.peixoto@wsu.edu marcos.frank@wsu.edu
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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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Posted November 08, 2018.
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Shank3 Modulates Sleep and Expression of Circadian Transcription Factors
Ashley M. Ingiosi, Taylor Wintler, Hannah Schoch, Kristan G. Singletary, Dario Righelli, Leandro G. Roser, Davide Risso, Marcos G. Frank, Lucia Peixoto
bioRxiv 465799; doi: https://doi.org/10.1101/465799
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Shank3 Modulates Sleep and Expression of Circadian Transcription Factors
Ashley M. Ingiosi, Taylor Wintler, Hannah Schoch, Kristan G. Singletary, Dario Righelli, Leandro G. Roser, Davide Risso, Marcos G. Frank, Lucia Peixoto
bioRxiv 465799; doi: https://doi.org/10.1101/465799

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