RT Journal Article
SR Electronic
T1 Mecp2 regulates <em>tnfa</em> during zebrafish embryonic development and acute inflammation
JF Disease Models &amp; Mechanisms
JO Dis Models Mech
FD The Company of Biologists Limited
SP 1439
OP 1451
DO 10.1242/dmm.026922
VO 10
IS 12
A1 van der Vaart, M.
A1 Svoboda, O.
A1 Weijts, B. G.
A1 Espín-Palazón, R.
A1 Sapp, V.
A1 Pietri, T.
A1 Bagnat, M.
A1 Muotri, A. R.
A1 Traver, D.
YR 2017
UL http://dmm.biologists.org/content/10/12/1439.abstract
AB 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.