The MAGEL2 gene appears as one of the main genes involved in feeding and behavioral (autistic like behavior) alterations observed in Prader-Willi Syndrome. We showed that, in mouse, the deficiency of Magel2 results in a phenotype similar to the clinical description of patients with mutations in MAGEL2. Indeed, we showed that Magel2-deficient mice display a deficiency of oxytocin at birth and are a pertinent model for Prader-Willi Syndrome, mimicking a disturbance in early feeding, with poor sucking activity, and later on in adulthood showing alterations in social behavior and learning abilities. Importantly, an administration of oxytocin in Magel2-deficient pups at birth restores a normal sucking activity and normalizes the social behavior and learning abilities in adulthood.
Our results suggest that, in Magel2 deficient mice, an administration of oxytocin in a critical period of post-natal development allows altered behavior to be corrected, even though a transient and partial rescue can follow an acute administration at any developmental stage. Thus, this model is perfectly suited for understanding the alterations of the OT-system in PWS and the rescue effect of an early exogenous OT administration. This concept opens the door to a powerful pharmacological therapy for the PWS and might be considered for other pathologies such as autism spectrum disorders.
However, the relationship between the inactivation of Magel2 and the alteration of the oxytocin system is not yet elucidated and needs further investigation. Furthermore we do not know how an administration of exogenous oxytocin acts during brain development to allow a long term effect in Magel2-KO mice. This project aims to increase our knowledge of these two last points contributing to an essential information for the development of adequate supplemental therapy in early infancy.
Wired for eating: how is an active feeding circuitry established in the postnatal brain? Muscatelli F, Bouret SGC. Current Opinion in Neurobiology. Volume 52: 165-171, 2018.
Francoise Muscatelli, PhD
$86,450 (In partnership with Prader-Willi France)
Mediterranean Institute of Neurobiology, INMED, France