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Brain Science Advances 2022, 8(3): 173-182 https://doi.org/10.26599/BSA.2022.9050012
Review Article | Open Access | Issue | Published: 27 May 2022

Hunt for mammalian sleep-regulating genes

Show Author's Information Hiromasa Funato1,2( ),  Masashi Yanagisawa1,3,4( )
 International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
 Department of Anatomy, Faculty of Medicine, Toho University, Ota-ku, Tokyo 951-8585, Japan
 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75390, Texas, USA
 Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan
Keywords:
mouse, sleep, forward genetics, reverse genetics, human, SIK3
Cite this article:
Funato H, Yanagisawa M. Hunt for mammalian sleep-regulating genes. Brain Science Advances, 2022, 8(3): 173-182. https://doi.org/10.26599/BSA.2022.9050012
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Abstract Full text About this article

Genetics is one of the various approaches adopted to understand and control mammalian sleep. Reverse genetics, which is usually applied to analyze sleep in gene-deficient mice, has been the mainstream field of genetic studies on sleep for the past three decades and has revealed that various molecules, including orexin, are involved in sleep regulation. Recently, forward genetic studies in humans and mice have identified gene mutations responsible for heritable sleep abnormalities, such as SIK3, NALCN, DEC2, the neuropeptide S receptor, and β1 adrenergic receptor. Furthermore, the protein kinase A-SIK3 pathway was shown to represent the intracellular neural signaling for sleep need. Large-scale genome-wide analyses of human sleep have been conducted, and many gene loci associated with individual differences in sleep have been found. The development of genome-editing technology and gene transfer by an adeno-associated virus has updated and expanded the genetic studies on mammals. These efforts are expected to elucidate the mechanisms of sleep–wake regulation and develop new therapeutic interventions for sleep disorders.


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About this article

Hunt for mammalian sleep-regulating genes

Show Author's information Hiromasa Funato1,2( ), Masashi Yanagisawa1,3,4( )
 International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
 Department of Anatomy, Faculty of Medicine, Toho University, Ota-ku, Tokyo 951-8585, Japan
 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75390, Texas, USA
 Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan

Abstract

Genetics is one of the various approaches adopted to understand and control mammalian sleep. Reverse genetics, which is usually applied to analyze sleep in gene-deficient mice, has been the mainstream field of genetic studies on sleep for the past three decades and has revealed that various molecules, including orexin, are involved in sleep regulation. Recently, forward genetic studies in humans and mice have identified gene mutations responsible for heritable sleep abnormalities, such as SIK3, NALCN, DEC2, the neuropeptide S receptor, and β1 adrenergic receptor. Furthermore, the protein kinase A-SIK3 pathway was shown to represent the intracellular neural signaling for sleep need. Large-scale genome-wide analyses of human sleep have been conducted, and many gene loci associated with individual differences in sleep have been found. The development of genome-editing technology and gene transfer by an adeno-associated virus has updated and expanded the genetic studies on mammals. These efforts are expected to elucidate the mechanisms of sleep–wake regulation and develop new therapeutic interventions for sleep disorders.

Keywords: mouse, sleep, forward genetics, reverse genetics, human, SIK3

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Publication history
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Publication history

Received: 12 March 2022
Revised: 14 April 2022
Accepted: 22 April 2022
Published: 27 May 2022
Issue date: September 2022

Copyright

© The authors 2022.

Acknowledgements

We thank all Yanagisawa/Funato laboratory members and IIIS members for their kind support, technical assistance, and discussion.

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