Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus - Archive ouverte HAL Access content directly
Journal Articles Human Molecular Genetics Year : 2012

Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus

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Carlos Dombret
  • Function : Author
Tuan Nguyen
  • Function : Author
Olivier Schakman
  • Function : Author
Jacques L. Michaud
  • Function : Author
Mathieu J. M. Bertrand
  • Function : Author
Olivier de Backer

Abstract

MAGED1, NECDIN and MAGEL2 are members of the MAGE gene family. The latter two of these genes have been involved in PraderWilli syndrome (PWS), which includes hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. Here, we show that Maged1-deficient mice develop progressive obesity associated with hyperphagia and reduced motor activity. Loss of Maged1 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 Maged1 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 Maged1 is required for OT processing or stability. A decrease in mature OT levels in Maged1 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.

Dates and versions

hal-01542831 , version 1 (20-06-2017)

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Carlos Dombret, Tuan Nguyen, Olivier Schakman, Jacques L. Michaud, Helene Hardin-Pouzet, et al.. Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus. Human Molecular Genetics, 2012, 21 (21), pp.4703-4717. ⟨10.1093/hmg/dds310⟩. ⟨hal-01542831⟩
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