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Perinatal Imprintings and Neurodevelopmental Disorders

Muscatelli Lab

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Scientific Interest

Prader-Willi Syndrome (PWS) is a complex and rare neurogenetic disease characterized by a range of physiological, endocrine, cognitive and behavioural disturbances, which might be considered as a lack of adaptation of the organism to the environment. The cause of this disease is genetic and the candidate genes are all regulated by the genomic imprinting, a mechanism leading to a paternal expression of those genes, the maternal alleles being normally silenced. In our team, using mouse models genetically modified, we study the physiopathological and physiological role of two candidate genes involved in PWS: the Necdin and Magel2 genes; both genes belong to the same family of MAGE genes whose the function is still enigmatic.
Our project focused on the phenotype investigation of these mouse mutants. The abrogation of Necdin leads to a partial early post-natal lethality due to respiratory distress (in 30% of cases), to a growth retardation, sensory-motor defects and behavioural alterations. Cellular investigations of the sensory and motor deficits revealed that Necdin is an anti-apoptotic factor in developing sensory neurons and motor neurons. On the other hand, investigations of the breathing deficit in Necdin KO mice showed an alteration of the regulatory systems of the Respiratory Rhythm Generator (RRG); a dysfunction of the serotonergic system in Necdin-KO mice, known to play a crucial role in maturation and function of the central respiratory system, might be the cause of this deficit Magel2 paternal deletion results in a fatal neonatal failure to thrive due to feeding problems; this phenotype is rescued by oxytocin administration.
Our results show a crucial role of oxytocin in feeding behaviour at birth. Adult mutant mice bypassing this lethality display growth retardation, hormonal, metabolic and circadian activity alterations.These in vivo studies on mouse models are very important to understand the PWS. Beyond that, they reveal new physiological, cellular and molecular neuronal pathways involve in vital functions, which might be altered in other diseases.

Scientific Projects

  • aOxytocinergic Alterations
  • bSerotonopathy
  • cGenetics and Epigenetics

Oxytocinergic Alterations

Role of Magel2 in the development of oxytocin network neuroarchitecture



Role of Necdin in the development of amine network neuroarchitecture


Genetics and Epigenetics

Expression of the maternal allele – gene therapy

In Brief

Key words

Genomic imprinting, Prader-Willi, Necdin, Magel2, oxytocin, feeding behaviour, serotonin, respiratory distress.

Experimental Approaches

Creation and studies of mouse models genetically modified. Histology, cellular and molecular biology, imaging, stereotaxia and virus injection .



Dr Pascale Durbec, Institut de Biologie du Développement de Marseille, IBDM, France
Dr Claude Villard, Protéomique et Innovation Technologique Timone, MaP-IBiSA platform, Marseille, France

National :

Pr. Maithe Tauber, Service Pédiatrie CHU Purpan Toulouse, France
Dr Michel Désarménien, Institut de Génomique Fonctionnel, IGF, Montpellier, France
Dr laurent Bezin, Centre de Recherche en Neurosciences de Lyon, CRNL, France

International :

Dr Bice Chini, Université de Milan, Italie
Dr Valery Grinewich, Max Plant Institute, Allemagne
Dr Rachel Wevrick, Université de l’Alberta, Canada



ANR: Programme Blanc , PRAGEDER 2009-2013
Associaton Prader-Willi France: 2014
Fondation Américaine Prader-Willi: 2014
Fondation Le Jeune: 2013-2014
ANR: Programme Bien être et Santé: PRADOX 2014-2018


Join our team

Our Team has open positions for undergraduate students, PhD students and post-doctoral fellows. Applications should be sent to francoise.muscatelli@inserm.fr

Our publications