GNAO1 and Encephalopathy: To establish a GNAO1 encephalopathy model in the fruit fly, we applied the CRISPR-Cas9 mutagenesis together with phiC31-mediated recombinase-mediated cassette exchange (RMCE) (41) to introduce the pathogenic G203R mutation into the Drosophila Gαo (see Materials and Methods and fig.