ZFIN ID: ZDB-PUB-171011-7
Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation.
van der Vaart, M., Svoboda, O., Weijts, B.G., Espín-Palazón, R., Sapp, V., Pietri, T., Bagnat, M., Muotri, A.R., Traver, D.
Date: 2017
Source: Disease models & mechanisms   10(12): 1439-1451 (Journal)
Registered Authors: Bagnat, Michel, Pietri, Thomas, Traver, David, van der Vaart, Michiel, Weijts, Bart
Keywords: Inflammation, Mecp2, Tnfa, Zebrafish
Microarrays: GEO:GSE80348
MeSH Terms:
  • Animals
  • Embryonic Development/genetics*
  • Gastrointestinal Tract/pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Inflammation/embryology*
  • Inflammation/genetics*
  • Inflammation Mediators/metabolism
  • Larva/growth & development
  • Leukocyte Count
  • Methyl-CpG-Binding Protein 2/deficiency
  • Methyl-CpG-Binding Protein 2/metabolism*
  • Neutrophils/pathology
  • Phenotype
  • Rett Syndrome/genetics
  • Rett Syndrome/pathology
  • Sequence Analysis, RNA
  • Tumor Necrosis Factor-alpha/genetics*
  • Tumor Necrosis Factor-alpha/metabolism
  • Zebrafish/embryology*
PubMed: 28993314 Full text @ Dis. Model. Mech.
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.