Mutation of the key residue for extraribosomal function of ribosomal protein S19 cause increased grooming behaviors in mice

•Gln137Glu-RP S19 knock-in mice show increased grooming behavior.•Gln137Glu-RP S19 knock-in mice show enhanced anxiety-like behavior.•Gln137Glu-RP S19 knock-in mice show enhanced fear memory.

Ribosomal protein S19 (RP S19) possesses ribosomal function as RP S19 monomer and extraribosomal function as cross-linked RP S19 oligomers which function as a ligand of the complement 5a (C5a) receptor (CD88). We have generated a Gln137Glu-RP S19 knock-in (KI) mouse, which is shown to possess the weakened extraribosomal function of RP S19. Because whether the extraribosomal function of RP S19 has a role in brain function had been unclear, we performed behavioral analysis on these mice and demonstrated that KI mice displayed an increased grooming behavior during open-field test and elevated plus maze test and an enhanced freezing behavior in contextual fear conditioning test. These results suggest an involvement of RP S19 oligomers in some anxiety-like behavior, especially grooming behavior.