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.
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Altered levels of OXT and OXTR in specific brain regions have been reported in animal models of psychiatric and neurodevelopmental disorders.
“Altered levels of OXT and OXTR in specific regions of the brain have been reported in a number of animal models of psychiatric and neurodevelopmental disorders [116-119].”
From Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice (2019) · cites this paper as [116]
Mice with a genetic disruption that models Prader-Willi syndrome usually exhibit a lethal feeding deficiency; this deficiency can be rescued with an injection of oxytocin on postnatal day 0, or induced in wild-type mice by injecting an oxytocin receptor antagonist 1-1.5 hours after birth.
“Male and female mice with a genetic disruption that models Prader–Willi syndrome usually exhibit a lethal feeding deficiency. This feeding deficiency can be rescued with an injection of Oxt on PND0, or induced in wild-type mice by injecting an OTA 1–1.5 h after birth (64).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [64]
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- Authors
- Schaller, F., Watrin, F., Sturny, R., Massacrier, A., Szepetowski, P., & Muscatelli, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institute of Biology of Development of Marseille Luminy, CNRS UMR 6126 and
- Inserm (FR)
- Corresponding author
- Muscatelli, Françoise
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-09-28
- Volume
- 19
- Issue
- 24
- Pages
- 4895-4905
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2167224770
- Cited by
- 234
- References
- 59
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 12 · 2023: 20 · 2022: 23 · 2021: 20 · 2020: 18 · 2019: 19 · 2018: 13 · 2017: 15 · 2016: 18 · 2015: 10 · 2014: 16 · 2013: 9 · 2012: 10
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- Prader-Willi syndrome, MAGEL2, imprinted genes, oxytocin, neonatal feeding, suckling behavior, hypothalamus, oxytocin receptor antagonist, mouse model, neonatal mortality
- MeSH terms
- Orexins, Animals, Animals, Newborn, Animals, Suckling, Antigens, Neoplasm, Feeding Behavior, Female, Hypothalamus, Immunohistochemistry, Injections, Subcutaneous, Male, Mutation, Neurons, Neuropeptides, Neurosecretory Systems, Oxytocin, Phenotype, Proteins, Vasopressins, Receptors, Oxytocin, Mice, Knockout, Gene Targeting, Genomic Imprinting, Intracellular Signaling Peptides and Proteins, Mice, Intrinsically Disordered Proteins
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