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

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 behavior 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.

SUBMITTER: Hebras J

PROVIDER: S-EPMC7673782 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Hebras Jade J Marty Virginie V Personnaz Jean J Mercier Pascale P Krogh Nicolai N Nielsen Henrik H Aguirrebengoa Marion M Seitz Hervé H Pradere Jean-Phillipe JP Guiard Bruno P BP Cavaille Jérôme J

eLife 20201005

<i>SNORD115</i> 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 <i>SNORD115</i> 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 ...[more]

PMID: 33016258

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Dataset Information

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

Publications

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

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