Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation.

Autor:	van der Vaart M; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA., Svoboda O; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA., Weijts BG; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA., Espín-Palazón R; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA., Sapp V; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA., Pietri T; Federated Department of Biological Sciences, New Jersey Institute of Technology, Newark, 07102 NJ, USA., Bagnat M; Department of Cell Biology, Duke University, Durham, 27708 NC, USA., Muotri AR; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA.; Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California San Diego, La Jolla, 92093 CA, USA., Traver D; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA dtraver@ucsd.edu.; Section of Cell and Developmental Biology, Division of Biological Sciences, University of California San Diego, La Jolla, 92093 CA, USA.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2017 Dec 19; Vol. 10 (12), pp. 1439-1451. Date of Electronic Publication: 2017 Dec 19.
DOI:	10.1242/dmm.026922
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2017. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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