ArticlePLoS genetics2013
Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Recommendations for the investigation of animal models of Prader-Willi syndrome.Mammalian genome : official journal of the International Mammalian Genome Society · 2013Guideline
- Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity.Molecular therapy. Advances · 2026Article
- Investigation of a mouse model of Prader-Willi Syndrome with combined disruption of Necdin and Magel2.JCI insight · 2025Article
- Environmental Enrichment Normalizes Metabolic Function in the Murine Model of Prader-Willi Syndrome Magel2-Null Mice.Endocrinology · 2025Article
- Control of tuberal hypothalamic development and its implications in metabolic disorders.Nature reviews. Endocrinology · 2025Review
- MAGEL2 (patho-)physiology and Schaaf-Yang syndrome.Developmental medicine and child neurology · 2025Review
- Article
- AAV-BDNF gene therapy ameliorates a hypothalamic neuroinflammatory signature in theMolecular therapy. Methods & clinical development · 2023Article
- Hormonal Imbalances in Prader-Willi and Schaaf-Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals.International journal of molecular sciences · 2023Review
- Early onset critically ill infants with Schaaf-Yang syndrome: a retrospective study from the China neonatal genomes project and literature review.Annals of translational medicine · 2023Article
- Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in theMolecular therapy. Methods & clinical development · 2022Article
- Article
- Leptin signaling and leptin resistance.Medical review (2021) · 2022Review
- Mechanisms of reduced leptin-mediated satiety signaling during obesity.International journal of obesity (2005) · 2022Article
- Do the diverse phenotypes of Prader-Willi syndrome reflect extremes of covariation in typical populations?Frontiers in genetics · 2022Article
- Resequencing and Signatures of Selective Scans Point to Candidate Genetic Variants for Hair Length Traits in Long-Haired and Normal-Haired Tianzhu White Yak.Frontiers in genetics · 2022Article
- Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells.Cell stem cell · 2021Article
- From leptin to lasers: the past and present of mouse models of obesity.Expert opinion on drug discovery · 2021Article
- Hypothalamic neuropeptides and neurocircuitries in Prader Willi syndrome.Journal of neuroendocrinology · 2021Review
- A Comprehensive Review of Genetically Engineered Mouse Models for Prader-Willi Syndrome Research.International journal of molecular sciences · 2021Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Prader-Willi Syndrome is the most common syndromic form of human obesity and is caused by the loss of function of several genes, including MAGEL2. Mice lacking Magel2 display increased weight gain with excess adiposity and other defects suggestive of hypothalamic deficiency. We demonstrate Magel2-null mice are insensitive to the anorexic effect of peripherally administered leptin. Although their excessive adiposity and hyperleptinemia likely contribute to this physiological leptin resistance, we hypothesized that Magel2 may also have an essential role in intracellular leptin responses in hypothalamic neurons. We therefore measured neuronal activation by immunohistochemistry on brain sections from leptin-injected mice and found a reduced number of arcuate nucleus neurons activated after leptin injection in the Magel2-null animals, suggesting that most but not all leptin receptor-expressing neurons retain leptin sensitivity despite hyperleptinemia. Electrophysiological measurements of arcuate nucleus neurons expressing the leptin receptor demonstrated that although neurons exhibiting hyperpolarizing responses to leptin are present in normal numbers, there were no neurons exhibiting depolarizing responses to leptin in the mutant mice. Additional studies demonstrate that arcuate nucleus pro-opiomelanocortin (POMC) expressing neurons are unresponsive to leptin. Interestingly, Magel2-null mice are hypersensitive to the anorexigenic effects of the melanocortin receptor agonist MT-II. In Prader-Willi Syndrome, loss of MAGEL2 may likewise abolish leptin responses in POMC hypothalamic neurons. This neural defect, together with increased fat mass, blunted circadian rhythm, and growth hormone response pathway defects that are also linked to loss of MAGEL2, could contribute to the hyperphagia and obesity that are hallmarks of this disorder.
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