Generation of the Nacc1+/R284W mouse model The mutant mice were generated by the Harvard University Mouse Genome Core through a collaboration of senior investigators M.D. of Massachusetts General Hospital (MGH) and M.B. and N.A. at the University of Massachusetts Chan Medical School (UMass Chan). Utilizing CRISPR/Cas9, homologous nucleotide substitutions were introduced into the Nacc1 gene (human: rs1060505041, cDNA 892C>T, p.298R>W; mouse: cDNA 850C>T and 852T>G, p284R>W; Fig. 1).