Impaired melanocortin pathway function in Prader-Willi syndrome gene-Magel2 deficient mice

Hum Mol Genet. 2018 Sep 15;27(18):3129-3136. doi: 10.1093/hmg/ddy216.


Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder causing social and learning deficits, impaired satiety and severe childhood obesity. Genetic underpinning of PWS involves deletion of a chromosomal region with several genes, including MAGEL2, which is abundantly expressed in the hypothalamus. Of appetite regulating hypothalamic cell types, both AGRP and POMC-expressing neurons contain Magel2 transcripts but the functional impact of its deletion on these cells has not been fully characterized. Here, we investigated these key neurons in Magel2-null mice in terms of the activity levels at different energy states as well as their behavioral function. Using cell type specific ex vivo electrophysiological recordings and in vivo chemogenetic activation approaches we evaluated impact of Magel2 deletion on AGRP and POMC-neuron induced changes in appetite. Our results suggest that POMC neuron activity profile as well as its communication with downstream targets is significantly compromised, while AGRP neuron function with respect to short term feeding is relatively unaffected in Magel2 deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / genetics*
  • Animals
  • Antigens, Neoplasm / genetics*
  • Appetite / genetics*
  • Appetite / physiology
  • Chromosome Deletion
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Hypothalamus / metabolism
  • Hypothalamus / pathology
  • Mice
  • Mice, Knockout
  • Neurons / pathology
  • Obesity / complications
  • Obesity / genetics
  • Obesity / physiopathology
  • Prader-Willi Syndrome / complications
  • Prader-Willi Syndrome / genetics*
  • Prader-Willi Syndrome / physiopathology
  • Pro-Opiomelanocortin / genetics*
  • Proteins / genetics*


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Antigens, Neoplasm
  • Magel2 protein, mouse
  • Proteins
  • Pro-Opiomelanocortin