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- Title
Loss of Magedl results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus.
- Authors
Dombret, Carlos; Nguyen, Tuan; Schakman, Olivier; Michaud, Jacques L.; Hardin-Pouzet, Hélène; Bertrand, Mathieu J. M.; De Backer, Olivier
- Abstract
MAGED1, NECDIN and MAGEL2 are members of the MAGE gene family. The latter two of these genes have been involved in Prader-Willi syndrome (PWS), which includes hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. Here, we show that Magedi-deficient mice develop progressive obesity associated with hyperphagia and reduced motor activity. Loss of Magedl also results in a complex behavioral syndrome that includes reduced social interactions and memory, deficient sexual behavior, as well as increased anxiety and self-grooming. Oxytocin (OT), which is produced in the hypothalamus, can act as a neurotransmitter that reduces anxiety, promotes social behaviors and regulates food intake. Growing evidences indicate that OT is involved in autism. We found that Magedl mutants showed a severe reduction in the levels of mature OT, but not of its precursors, in the hypothalamus. Moreover, the administration of OT rescued the deficit in social memory of these mice. We conclude that Magedl is required for OT processing or stability. A decrease in mature OT levels in Magedl mutants affects social interactions and possibly other behavioral processes. Our observations suggest that, in human, MAGED1 could play a role in autism or cause a neurodevelopmental condition that is reminiscent of the PWS.
- Publication
Human Molecular Genetics, 2012, Vol 21, Issue 21, p4703
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/dds310