Behavioral Characterization of System xc- Mutant Mice

System xc- is a membrane-bound transporter that exchanges one glutamate for intake of a cystine molecule. It is thought to be important in regulating extracellular glutamate levels, postsynaptic receptor abundance/tone and synaptic plasticity. All three of these things should contribute to how an animal behaves, and therefore loss of this transporter should have drastic effects of behavior. Specifically we studied motor behaviors using a rotarod task and open field maze and learning behaviors using a three-arm and four-arm spontaneous alternation task. We tested behavior across three different genotypes of system xc- knockout and in both males and females. We showed that sut mice have altered spontaneous alternation ability in both three and four-arm spontaneous alternation tasks and reduced movement in the open field maze, but xCT and xCT/sut strains do not have impairments in these tasks compared to their backgrounds. We also found that all three strains were complete protein level knockouts of the xCT protein and that sut and xCT/sut mice did not have reduced glutamate levels in the striatum and cerebellum compared to their backgrounds. Therefore it appears that if there is a relationship between loss of system xc- and behavior, it is very subtle. There may also be other mechanisms that relate to compensation in glutamate levels in sut mice.