|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.
|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|
|PubMed:||28993314 Full text @ Dis. Model. Mech.|
van der Vaart, M., Svoboda, O., Weijts, B.G., Espín-Palazón, R., Sapp, V., Pietri, T., Bagnat, M., Muotri, A.R., Traver, D. (2017) Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation.. Disease models & mechanisms. 10(12):1439-1451.
ABSTRACTMutations 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.