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Adult-onset deletion of the Prader-Willi syndrome susceptibility gene Snord116 in mice results in reduced feeding and increased fat mass


BACKGROUND: The imprinted small nucleolar RNA (snoRNA) Snord116 is implicated in the aetiology of Prader-Willi syndrome (PWS), a disease associated with hyperphagia and obesity. Germline deletion of Snord116 in mice has been found to lead to increased food intake but not to the development of obesity. To determine the role of Snord116 independent of potential compensatory developmental factors, we investigated the effects of conditional adult-onset deletion of Snord116 in mice. METHODS: Deletion of Snord116 was induced at 8 weeks of age by oral administration of tamoxifen to male Snordlox/lox; ROSAcre/+ mice, with vehicle-treated mice used as controls. Body weight (BW) was monitored weekly and body composition was measured by dual-energy X-ray absorptiometry and tissue dissection. Non-fasted and fasting-induced food intake was determined, and glucose and insulin tolerance tests were performed. Twenty-four-hour energy expenditure and physical activity were assessed by indirect calorimetry. RESULTS: Adult-onset deletion of Snord116 led to reduced food intake and increased adiposity, albeit with no concomitant change in BW or lean mass compared to controls. Adult onset Snord116 deletion was also associated with worsened glucose tolerance and insulin sensitivity. CONCLUSIONS: This study identified a key role for Snord116 in feeding behaviour and growth. Further, it is likely that the effects of this gene are modulated by developmental stage, as mice with adult-onset deletion showed an opposite phenotype, with respect to food intake and body composition, to previously published data on mice with germline deletion.

Type Journal
ISBN 2224-4344 (Print) 2224-4336 (Linking)
Authors Purtell, L.; Qi, Y.; Campbell, L.; Sainsbury, A.; Herzog, H.
Responsible Garvan Author Prof Herbert Herzog
Publisher Name Translational Pediatrics
Published Date 2017-04-16
Published Volume 6
Published Issue 2
Published Pages 88-97
Status Published in-print
DOI 10.21037/tp.2017.03.06
URL link to publisher's version
OpenAccess link to author's accepted manuscript version