title: A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mouse newborns deficient for the imprinted Magel2 gene.
abstract: The onset of feeding at birth is a vital step for the adaptation of the neonate to extra uterine life. Prader-Willi syndrome (PWS) is a complex neurogenetic disorder caused by the alteration of several imprinted contiguous genes including MAGEL2. PWS presents with various clinical manifestations, including poor suckling behaviour and feeding problems in neonates. Hypothalamic defects have been proposed, but the pathophysiological mechanisms remain poorly understood. Here, we report that a Magel2-deficient mouse with 50% neonatal mortality had an altered onset of suckling activity and subsequent impaired feeding, suggesting a role of MAGEL2 in the suckling deficit seen in PW newborns. The hypothalamus of Magel2 mutant neonates showed a significant reduction in oxytocin (OT). Furthermore, injection of a specific OT receptor antagonist in wild-type neonates recapitulated the feeding deficiency seen in Magel2 mutants, and a single injection of OT, 3-5 h after birth, rescued the phenotype of Magel2 mutant pups, allowing all of them to survive. Our study illustrates the crucial role of feeding onset behaviour after birth. We propose that OT supply might constitute a promising avenue for the treatment of feeding difficulties in PW neonates and potentially of other newborns with impaired feeding onset.
authors.affiliation: Institute of Biology of Development of Marseille Luminy, CNRS UMR 6126, INSERM U901, Parc Scientifique de Luminy, BP 13, 13273 Marseille Cedex 09, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Schaller
authors.forename: Françoise
authors.initials: F
authors.lastname: Watrin
authors.forename: Rachel
authors.initials: R
authors.lastname: Sturny
authors.forename: Annick
authors.initials: A
authors.lastname: Massacrier
authors.forename: Pierre
authors.initials: P
authors.lastname: Szepetowski
authors.forename: Françoise
authors.initials: F
authors.lastname: Muscatelli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D018390:Gene Targeting; D018392:Genomic Imprinting / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology; D000068797:Orexins; D010121:Oxytocin / Q000008:administration & dosage* / Q000494:pharmacology*; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D014667:Vasopressins / Q000378:metabolism; D064267:Intrinsically Disordered Proteins
chemical_list: D000951:Antigens, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010121:Oxytocin; D011506:Proteins; D018045:Receptors, Oxytocin; D014667:Vasopressins; C403091:Magel2 protein, mouse; D064267:Intrinsically Disordered Proteins