Deletion of Mecp2 in Sim1-Expressing Neurons Reveals a Critical Role for MeCP2 in Feeding Behavior, Aggression, and the Response to Stress

Sharyl L. Fyffe, Jeff L. Neul, Rodney C. Samaco, Hsiao Tuan Chao, Shay Ben-Shachar, Paolo Moretti, Bryan E. McGill, Evan H. Goulding, Elinor Sullivan, Laurence H. Tecott, Huda Y. Zoghbi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

179 Scopus citations

Abstract

Rett Syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). In order to map the neuroanatomic origins of the complex neuropsychiatric behaviors observed in patients with RTT and to uncover endogenous functions of MeCP2 in the hypothalamus, we removed Mecp2 from Sim1-expressing neurons in the hypothalamus using Cre-loxP technology. Loss of MeCP2 in Sim1-expressing neurons resulted in mice that recapitulated the abnormal physiological stress response that is seen upon MeCP2 dysfunction in the entire brain. Surprisingly, we also uncovered a role for MeCP2 in the regulation of social and feeding behaviors since the Mecp2 conditional knockout (CKO) mice were aggressive, hyperphagic, and obese. This study demonstrates that deleting Mecp2 in a defined brain region is an excellent approach to map the neuronal origins of complex behaviors and provides new insight about the function of MeCP2 in specific neurons.

Original languageEnglish (US)
Pages (from-to)947-958
Number of pages12
JournalNeuron
Volume59
Issue number6
DOIs
StatePublished - Sep 25 2008

Keywords

  • HUMDISEASE
  • MOLNEURO
  • SYSNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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