Mutations in Adenosine deaminase acting on RNA (ADAR1) give rise to Aicardi-Goutières syndrome 6 (AGS6) a severe autoimmune disease characterized by inflammatory encephalopathy that presents within the first year of life. Some of the signs of AGS6 are microcephaly, calcifications in basal ganglia and other brain regions, abnormalities in the white matter tracts, excess lymphocytes in the cerebrospinal fluid (CSF) and increased interferon-alpha activation. Adar∆2-13 mutant mice lacking the Adar1 protein have aberrant high-level interferon expression and are embryonically lethal (E12.5). Adar∆2-13 Mavs double mutants in which the aberrant interferon induction is rescued, die within P10-15. Because the molecular mechanism of inflammatory encephalopathy in AGS6 has not been well defined, we examined brains of Adar Mavs double mutants via mass spectrometry and immunohistochemistry at P14. The proteomics analysis preliminary results show a significant downregulation of P2ry12, P2ry13, Aif1 (Iba1) and Tmem119 in Adar Mavs double mutants compared to the WT controls, indicative of microglial activation. Furthermore, decreased immunoreactivity of Iba1 in the Dorsal Striatum, Hippocampus, Thalamus, Corpus Callosum and Substantia Nigra in the Adar Mavs mutant brains confirms the proteomic analysis results. Interestingly, we found that these changes are rescued in Adar Mavs Eif2ak2 (gene encoding Pkr) triple mutants, suggesting that Pkr mediates the aberrant activation of microglia in brains of Adar Mavs mutants. In the future it would be interesting to determine if human PKR played a similar role in AGS6 patients, as this may pave the way for novel treatment of the disease.