Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation.

Journal Article (Journal Article)

Mutations in MECP2 cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of MECP2 also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MECP2 in controlling immune and inflammatory responses. Here, we used mecp2-null zebrafish to study the potential function of Mecp2 as an immunological regulator. Mecp2 deficiency resulted in an increase in neutrophil infiltration and upregulated expression of the pro- and anti-inflammatory cytokines Il1b and Il10 as a secondary response to disturbances in tissue homeostasis. By contrast, expression of the proinflammatory cytokine tumor necrosis factor alpha (Tnfa) was consistently downregulated in mecp2-null animals during development, representing the earliest developmental phenotype described for MECP2 deficiency to date. Expression of tnfa was unresponsive to inflammatory stimulation, and was partially restored by re-expression of functional mecp2 Thus, Mecp2 is required for tnfa expression during zebrafish development and inflammation. Finally, RNA sequencing of mecp2-null embryos revealed dysregulated processes predictive for Rett syndrome phenotypes.

Full Text

Duke Authors

Cited Authors

  • van der Vaart, M; Svoboda, O; Weijts, BG; Espín-Palazón, R; Sapp, V; Pietri, T; Bagnat, M; Muotri, AR; Traver, D

Published Date

  • December 19, 2017

Published In

Volume / Issue

  • 10 / 12

Start / End Page

  • 1439 - 1451

PubMed ID

  • 28993314

Pubmed Central ID

  • PMC5769600

Electronic International Standard Serial Number (EISSN)

  • 1754-8411

Digital Object Identifier (DOI)

  • 10.1242/dmm.026922


  • eng

Conference Location

  • England