Re-assessment of the involvement of Snord115 in the serotonin 2C receptor pathway in a genetically relevant mouse model - Archive ouverte HAL Access content directly
Journal Articles eLife Year : 2020

Re-assessment of the involvement of Snord115 in the serotonin 2C receptor pathway in a genetically relevant mouse model

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Jade Hebras
  • Function : Author
Virginie Marty
  • Function : Author
  • PersonId : 950075
Jean Personnaz
Nicolai Krogh
  • Function : Author
Henrik Nielsen
  • Function : Author
Marion Aguirrebengoa
  • Function : Author
Hervé Seitz
  • Function : Author
Jean-Phillipe Pradere
  • Function : Author
Bruno P Guiard
  • Function : Author
Jérôme Cavaille
  • Function : Author

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.

Dates and versions

hal-03019031 , version 1 (23-11-2020)

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Jade Hebras, Virginie Marty, Jean Personnaz, Pascale Mercier, Nicolai Krogh, et al.. Re-assessment of the involvement of Snord115 in the serotonin 2C receptor pathway in a genetically relevant mouse model. eLife, 2020, 9, pp.e60862. ⟨10.7554/eLife.60862⟩. ⟨hal-03019031⟩
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