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Dis Model Mech. 2017 Dec 19;10(12):1439-1451. doi: 10.1242/dmm.026922.

Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation.

Author information

1
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA.
2
Federated Department of Biological Sciences, New Jersey Institute of Technology, Newark, 07102 NJ, USA.
3
Department of Cell Biology, Duke University, Durham, 27708 NC, USA.
4
Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California San Diego, La Jolla, 92093 CA, USA.
5
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, 92093 CA, USA dtraver@ucsd.edu.
6
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California San Diego, La Jolla, 92093 CA, USA.

Abstract

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.

KEYWORDS:

Inflammation; Rett syndrome; Zebrafish; mecp2; tnfa

PMID:
28993314
PMCID:
PMC5769600
DOI:
10.1242/dmm.026922
[Indexed for MEDLINE]
Free PMC Article

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