Magel2-null mice are hyper-responsive to setmelanotide, a melanocortin 4 receptor agonist.

ABSTRACT:

Background and purpose

α- and β-melanocyte-stimulating hormones (MSH) are derived from pro-opiomelanocortin (POMC) and are the natural agonist ligands of the melanocortin 4 receptor, a key regulator of energy homeostasis. Recent rodent and human data have implicated the MAGEL2 gene, which may regulate activation of POMC neurons, as a significant contributor to the metabolic symptoms observed in Prader-Willi Syndrome (PWS). Firstly, patients with protein truncating mutations in MAGEL2 exhibit numerous clinical characteristics of PWS. Secondly, Magel2-null mice may not normally activate MC4 receptors, as they are defective in the activation of their POMC neurons and hence may fail to normally release the POMC-derived MC4 receptor agonist ligands α- and β-MSH. Magel2-null mice represe

SUBMITTER: Bischof JM 

PROVIDER: S-EPMC4978157 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature