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April 2026 Mouse of the Month |
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The Crhbp Gene involved in REM Sleep C57BL/6J-Crhbp<em1(cre)Sleep> (RBRC12542)
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| Corticotropin-releasing hormone-binding protein (CRHBP) regulates corticotropin-releasing hormone activity and is involved in stress responses and hormonal regulation. Dr. Yu Hayashi and his colleagues generated a Crhbp Cre driver KI mouse strain (RBRC12542), in which a P2A-Cre-polyA cassette is inserted immediately upstream of the stop codon of the Crhbp gene. This design ensures that Cre recombinase expression is controlled by the endogenous Crhbp promoter. The strain was generated with support from the Laboratory Animal Resource Center at the University of Tsukuba. Using this strain, depositors demonstrated that CRHBP is strongly expressed in the sublaterodorsal tegmental nucleus (SubLDT) within the dorsal pons. They also found that activation of CRHBP-positive neurons projecting to the medulla induces REM sleep. Moreover, they found that CRHBP-positive neurons form neural circuits that connect to motor neurons controlling skeletal muscles via the spinal cord, thereby promoting muscle atonia during REM sleep [1,2]. Furthermore, using an in vivo neuronal spike recording technique called opto-tagging, they recorded the single unit activity of CRHBP-positive neurons from the brain of sleeping mice. This revealed that many CRHBP-positive neurons are maximally active during REM sleep [3,4]. Abnormalities in REM sleep are associated with dementia, cardiovascular disease, and Parkinson’s disease. By analysis of CRHBP-positive neurons using this strain, the mechanisms underlying REM sleep are expected to be further elucidated, potentially leading to the prevention and treatment of diseases associated with REM sleep abnormalities. |
| Keywords | : | CRHBP, REM sleep, Cre driver mice, muscle atonia, Parkinson’s disease | |
| Depositors | : | Yu Hayashi, Ph.D., Mitsuaki Kashiwagi, Ph.D., and Mika Kanuka, Ph.D. (University of Tsukuba) | |
| Strain name | : | C57BL/6J-Crhbp<em1(cre)Sleep> | |
| RBRC No. | : | RBRC12542 | |
| References | : | [1] | Kashiwagi M, Beck G, Kanuka M, Arai Y, Tanaka K, Tatsuzawa C, Koga Y, Saito YC, Takagi M, Oishi Y, Sakaguchi M, Baba K, Ikuno M, Yamakado H, Takahashi R, Yanagisawa M, Murayama S, Sakurai T, Sakai K, Nakagawa Y, Watanabe M, Mochizuki H, Hayashi Y. A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson’s disease. Cell. 2024 Oct 31;187(22):6272-6289.e21. |
| [2] | Elucidation of the Neural Circuitry Inducing REM Sleep and Investigation of the Cause of REM Sleep Behavior Disorder 2024.10.4 University of Tsukuba Research News |
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| [3] | Arai Y, Kashiwagi M, Kanda T, Koyanagi I, Sakaguchi M, Yanagisawa M, Koyama Y, Hayashi Y. Diverse Firing Profiles of Crhbp-positive Neurons in the Dorsal Pons Suggestive of Their Pleiotropic Roles in REM Sleep Regulation in Mice. J Neurosci. 2025 Jul 9;45(28):e2365242025. |
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| [4] | Identification of Neurons that Act as a Switch for REM Sleep, a Major Source of Dreams —Neurons active exclusively during REM sleep revealed after decades of mystery— 2025.06.24 The University of Tokyo Press Releases. |
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| April 2026 Saori Mizuno, Ph.D. Contact: Experimental Animal Division, RIKEN BioResource Research Center (animal.brc@riken.jp) All materials contained on this site may not be reproduced, distributed, displayed, published or broadcast without the prior permission of the owner of that content. |
