Reassessment of the involvement of Snord115 in the serotonin 2c receptor pathway in a genetically relevant mouse model

• Published in: eLife Vol. 9
• Main Authors: Hebras, Jade, Marty, Virginie, Personnaz, Jean, Mercier, Pascale, Krogh, Nicolai, Nielsen, Henrik, Aguirrebengoa, Marion, Seitz, Hervé, Pradere, Jean-Phillipe, Guiard, Bruno P, Cavaille, Jérôme
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 05.10.2020; eLife Sciences Publication; eLife Sciences Publications, Ltd; eLife Sciences Publications Ltd
• Subjects: alternative RNA splicing; Animal genetics; Animals; Behavior, Animal; Biochemistry, Molecular Biology; Chromosomes and Gene Expression; CRISPR-Cas Systems; Diet, High-Fat; eating disorder; Emotions; Feeding Behavior - physiology; Gene Expression Regulation - physiology; Genetics; Life Sciences; Messenger RNA; Mice; Mice, Knockout; Molecular Networks; Phenols (Class of compounds); Physiological aspects; Prader-Willi syndrome; Receptor, Serotonin, 5-HT2C - genetics; Receptor, Serotonin, 5-HT2C - metabolism; RNA editing; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Nucleolar - genetics; RNA, Small Nucleolar - metabolism; Serotonin; serotonin 2c receptor; snoRNA; eating disorder; mouse; RNA editing; serotonin 2c receptor; alternative RNA splicing; chromosomes; prader-willi syndrome; gene expression; snoRNA
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.60862

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 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 knockout mouse. Surprisingly, we uncovered only modest region-specific alterations in RNA editing profiles, while 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 behavior were also normal, even after exposure to high-fat diet. Our study raises questions concerning the physiological role of , notably its involvement in behavioural disturbance associated with PWS.