Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation
| Autor: | M. van der Vaart, O. Svoboda, B. G. Weijts, R. Espín-Palazón, V. Sapp, T. Pietri, M. Bagnat, A. R. Muotri, D. Traver |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Disease Models & Mechanisms, Vol 10, Iss 12, Pp 1439-1451 (2017) |
| Druh dokumentu: | article |
| ISSN: | 1754-8403 1754-8411 |
| DOI: | 10.1242/dmm.026922 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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