Re-assessment of the involvement of Snord115 in the serotonin 2C receptor pathway in a genetically relevant mouse model
- CNRS, France
- Inserm, France
- University of Copenhagen, Denmark
- CBI, UPS, CNRS, France
Abstract
SNORD115 has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base-pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because SNORD115 genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired emotional response and/or compulsive overeating characteristic of this disease. In order to test this appealing but never demonstrated hypothesis in vivo, we created a CRISPR/Cas9-mediated Snord115 knockout mouse. Surprisingly, we uncovered only modest region-specific alterations in Htr2c RNA editing profiles while Htr2c alternative RNA splicing was unchanged. These subtle changes, whose functional relevance remains uncertain, were not accompanied by any discernible defects in anxio-depressive-like phenotypes. Energy balance and eating behaviour were also normal, even after exposure to high fat diet. Our study raises questions concerning the physiological role of SNORD115, notably its involvement in behavioural disturbance associated with PWS.
Data availability
RiboMeth-seq data are available on GEO under the accession number GSE145159Raw data (mRNAseq) are available on Sequence Read Archive (SRA) database under the accession number PRJNA608249.Raw data (A-to-I RNA editing) are available on Sequence Read Archive (SRA) database under the accession numbers PRJNA603261 and PRJNA603264. Scripts used for that analysis, detailed instructions and intermediary data have been deposited at https://github.com/HKeyHKey/Hebras_et_al_2020
Article and author information
Author details
Funding
Fundation for Prader-Willi research
- Jérôme Cavaille
Fondation pour la Recherche Médicale (DEQ20160334936)
- Jérôme Cavaille
Agence Nationale de la Recherche (ANR-18-CE12-0008-01)
- Jérôme Cavaille
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal procedures were approved by the University of Toulouse and CNRS Institutional Animal Care Committee (DAP2016061716367988 and DAP2018011214542827). The animal housing facility met CNRS standards
Copyright
© 2020, Hebras et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Re-assessment of the involvement of Snord115 in the serotonin 2C receptor pathway in a genetically relevant mouse model
eLife 9:e60862.
https://doi.org/10.7554/eLife.60862
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