Correlation Engine 2.0
Clear Search sequence regions


  • amygdala (2)
  • BDNF (3)
  • brain (2)
  • factor (2)
  • glycogen (2)
  • gsk 3β (1)
  • humans (1)
  • igf 1 (3)
  • impairment (1)
  • knockout mice (2)
  • MeCP2 (13)
  • mecp2 protein (2)
  • methyl (3)
  • mice (6)
  • mrna (2)
  • protein gene (2)
  • signal (1)
  • wnt proteins (2)
  • Wnt6 (9)
  • β catenin (1)
  • Sizes of these terms reflect their relevance to your search.

    The methyl-CpG-binding protein 2 gene, MECP2, is an X chromosome-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). Previous study has shown that re-expression of SUMO-modified MeCP2 in Mecp2-null neurons rescues synaptic and behavioral deficits in Mecp2 conditional knockout mice, whereas about 12-fold decrease in Wnt6 mRNA level was found in MeCP2K412R sumo-mutant mice. Here, we examined the role of Wnt6 in MeCP2 T158A mouse model of RTT. Results show that lentiviral delivery of Wnt6 to the amygdala ameliorates locomotor impairment and social behavioral deficits in these animals. MeCP2 T158A mice show decreased level of GSK-3β phosphorylation and increased level of β-catenin phosphorylation. They also show reduced level of MeCP2 SUMOylation. These alterations were also restored by lenti-Wnt6 transduction. Further, both BDNF and IGF-1 expressions are decreased in MeCP2 T158A mice. Overexpression of Wnt6 increases Bdnf and Igf-1 promoter activity in HEK293T cells in a dose-dependent manner. Lenti-Wnt6 transduction to the amygdala similarly increases the mRNA level and protein expression of BDNF and IGF-1 in MeCP2 T158A mice. Moreover, environmental enrichment (EE) similarly ameliorates the locomotor and social behavioral deficits in MeCP2 T158A mice. One of the mechanisms underlying EE is mediated through enhanced MeCP2 SUMOylation and increased Wnt6 expression in these animals by EE.

    Citation

    Wei-Lun Hsu, Yun-Li Ma, Yen-Chen Liu, Derek J C Tai, Eminy H Y Lee. Restoring Wnt6 signaling ameliorates behavioral deficits in MeCP2 T158A mouse model of Rett syndrome. Scientific reports. 2020 Jan 23;10(1):1074

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 31974426

    View Full Text