Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity

Article

Asai, M., Ramachandrappa, S., Joachim, M., Shen, Y., Zhang, R., Nuthalapati, N., Ramanathan, V., Strochlic, D., Ferket, P., Linhart, K., Ho, C., Novoselova, T., Garg, S., Ridderstråle, M., Marcus, C., Hirschhorn, J., Keogh, J., O’Rahilly, S., Chan, L., Clark, A., Farooqi, S. and Majzoub, J. 2013. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science. 341 (6143), pp. 275-278. https://doi.org/10.1126/science.1233000
TypeArticle
TitleLoss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity
AuthorsAsai, M., Ramachandrappa, S., Joachim, M., Shen, Y., Zhang, R., Nuthalapati, N., Ramanathan, V., Strochlic, D., Ferket, P., Linhart, K., Ho, C., Novoselova, T., Garg, S., Ridderstråle, M., Marcus, C., Hirschhorn, J., Keogh, J., O’Rahilly, S., Chan, L., Clark, A., Farooqi, S. and Majzoub, J.
Abstract

Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed Melanocortin 2 Receptor Accessory Protein 2 (MRAP2), we characterized mice with whole body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with Melanocortin 4 Receptor (Mc4r), a protein previously implicated in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger cyclic AMP, suggesting that alterations in Mc4r signaling may be one mechanism underlying the association between Mrap2 disruption and obesity. In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans

PublisherAmerican Association for the Advancement of Science
JournalScience
ISSN0036-8075
Electronic1095-9203
Publication dates
Print02 Oct 2013
Online19 Jul 2013
Publication process dates
Deposited11 Nov 2019
Accepted19 Jul 2013
Output statusPublished
Digital Object Identifier (DOI)https://doi.org/10.1126/science.1233000
LanguageEnglish
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