Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome

Kerstin Ure, Hui Lu, Wei Wang, Aya Ito-Ishida, Zhenyu Wu, Ling Jie He, Yehezkel Sztainberg, Wu Chen, Jianrong Tang, Huda Y. Zoghbi

研究成果: Article査読

78 被引用数 (Scopus)

抄録

The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2+/- mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome.

本文言語English
論文番号e14198
ジャーナルeLife
5
JUN2016
DOI
出版ステータスPublished - 2016 6月 21
外部発表はい

ASJC Scopus subject areas

  • 神経科学一般
  • 免疫学および微生物学一般
  • 生化学、遺伝学、分子生物学一般

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