Citation:
Dis Model Mech. 2017 Oct 9. pii: dmm.026922. doi: 10.1242/dmm.026922. [Epub ahead of print]
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. In contrast, expression of the pro-inflammatory 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.
Epub:
Yes
Link to Publication:
http://dmm.biologists.org/content/10/12/1439
Organism or Cell Type:
zebrafish
Delivery Method:
microinjection