Dr. Tucci’s group has shown that mice with the SNORD116 deletion have sleep abnormalities and increased body temperature. They hypothesize that environmental temperature may play a crucial role in the pathophysiology of PWS symptoms including sleep and obesity. They will use PWS mice that will be maintained under different temperature regimens and then analyzed for sleep changes, body weight, food intake and energy expenditure.
ABTRACT: Prader-Willi Syndrome (PWS) is a rare genetic disorder that results from the absence of normally active paternally inherited genes at chromosome region 15q11-13, involving also microdeletions of Snord116 gene cluster. Interestingly, PWS locus in mice is highly homologous to that of humans. Indeed, mice with paternally inherited Snord116 deletions exhibit a subset of the classical clinical phenotype of humans PWS. For this reason, PWS mutant mice represent a suitable model to study PWS symptoms at the preclinical stage. PWS mutant mice may help to understand a future therapeutic approach to improve the quality of life of PWS patients.
In our laboratory PWS mutant mice showed hyperphagia, a significant increase in spontaneous food intake in presence of low body weight and fat mass compared to normal mice without deletion of Snord116. Moreover, these PWS mutant mice are characterised by sleep abnormalities and increase of body temperature.
Our hypothesis is that environmental temperature may play a crucial role in the pathophysiology of PWS symptoms. In particular, by controlling adaptive thermogenesis requirement can be permissive for the development of obesity by limiting increased energy expenditure required for maintaining core body temperature in mammals. To test this hypothesis we will use PWS mutant mice that will be maintained under different temperature regimen. Then EEG sleep changes, body weight, food intake and energy expenditure at different conditions will be assessed.
Valter Tucci, PhD
Italian Institute of Technology