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

    Research output: Contribution to journalArticle

    178 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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  • Cite this

    Fyffe, S. L., Neul, J. L., Samaco, R. C., Chao, H. T., Ben-Shachar, S., Moretti, P., McGill, B. E., Goulding, E. H., Sullivan, E., Tecott, L. H., & Zoghbi, H. Y. (2008). Deletion of Mecp2 in Sim1-Expressing Neurons Reveals a Critical Role for MeCP2 in Feeding Behavior, Aggression, and the Response to Stress. Neuron, 59(6), 947-958. https://doi.org/10.1016/j.neuron.2008.07.030