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.
- Jérôme Cavaille
- Jérôme Cavaille
- Jérôme Cavaille
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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
- Thomas R Gingeras, Cold Spring Harbor Laboratory, United States
- Received: July 8, 2020
- Accepted: September 22, 2020
- Accepted Manuscript published: October 5, 2020 (version 1)
© 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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