Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation

Mutations in cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MECP2 in controlling immune and inflammatory responses. Here, we used -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 -null animals during development, representing the earliest developmental phenotype described for MECP2 deficiency to date. Expression of was unresponsive to inflammatory stimulation, and was partially restored by re-expression of functional Thus, Mecp2 is required for expression during zebrafish development and inflammation. Finally, RNA sequencing of -null embryos revealed dysregulated processes predictive for Rett syndrome phenotypes.