Deletion of the Snord116/SNORD116 Alters Sleep in Mice and Patients with Prader-Willi Syndrome
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Updated: Apr 1, 2026
Noninvasive, High-throughput Determination of Sleep Duration in Rodents
Published on: April 18, 2018
Glenda Lassi1, Lorenzo Priano2, Silvia Maggi1
1Neuroscience and Brain Technologies (NBT) Department, Istituto Italiano di Tecnologia (IIT), via Morego 30, 16163 Genova (Italy).
Insights
Small nucleolar ribonucleic acid-116 (SNORD116) gene deletion causes sleep disturbances in Prader-Willi syndrome (PWS). This study found that SNORD116 is involved in regulating sleep and body temperature, offering insights into PWS sleep abnormalities.
Area of Science:
- Neuroscience
- Genetics
- Sleep Medicine
Background:
- Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder linked to chromosome 15q11-13 imprinting defects.
- Sleep-wake disturbances are common in PWS patients.
- Small nucleolar ribonucleic acid-116 (SNORD116) is a candidate gene for PWS, highly expressed in the brain.
Purpose of the Study:
- To investigate the role of SNORD116 in the sleep abnormalities characteristic of PWS.
- To test the hypothesis that SNORD116 is responsible for PWS-related sleep defects.
Main Methods:
- Studied sleep patterns (EEG, temperature) in Snord116 mutant mice (PWScr(m+/p-)) and wild-type littermates.
- Utilized high-resolution MRI to assess brain morphology in mutant mice.
- Analyzed EEG parameters in two PWS patients with SNORD116 deletions, comparing them to healthy and obese subjects.
Main Results:
- Snord116 mutant mice exhibited altered REM sleep and abnormal EEG theta waves.
- Identical sleep and EEG defects were observed in PWS patients with SNORD116 deletions.
- Reduced gray matter volume in the ventral hippocampus and septum was noted in mutant mice, correlating with EEG alterations.
- Mutant mice showed increased body temperature, consistent with sleep alterations.
Conclusions:
- Paternally expressed Snord116 plays a role in the 24-hour regulation of sleep physiology.
- SNORD116 is identified as a candidate gene for the sleep disturbances experienced by individuals with PWS.
Study Objectives:
Sleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome.
Methods:
We studied sleep in mutant mice that carry a deletion of Snord116 at the orthologous locus (mouse chromosome 7) of the human PWS critical region (PWScr). In particular, we assessed EEG and temperature profiles, across 24-h, in PWScr (m+/p-) heterozygous mutants compared to wild-type littermates. High-resolution magnetic resonance imaging (MRI) was performed to explore morphoanatomical differences according to the genotype. Moreover, we complemented the mouse work by presenting two patients with a diagnosis of PWS and characterized by atypical small deletions of SNORD116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects.
Results:
By studying the mouse mutant line PWScr(m+/p-), we observed specific rapid eye movement (REM) sleep alterations including abnormal electroencephalograph (EEG) theta waves. Remarkably, we observed identical sleep/EEG defects in the two PWS cases. We report brain morphological abnormalities that are associated with the EEG alterations. In particular, mouse mutants have a bilateral reduction of the gray matter volume in the ventral hippocampus and in the septum areas, which are pivotal structures for maintaining theta rhythms throughout the brain. In PWScr(m+/p-) mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients.
Conclusions:
Our study indicates that paternally expressed Snord116 is involved in the 24-h regulation of sleep physiological measures, suggesting that it is a candidate gene for the sleep disturbances that most individuals with PWS experience.
