Behavioral characterization of system xc- mutant mice.
The slc7a11 gene encodes xCT, an essential component of 'system xc-', a plasma membrane exchanger that imports cystine and exports glutamate. Slc7a11 is expressed primarily in the brain, but its role there is not clear. We performed behavioral tests on two different strains of homozygous slc7a11 mutant mice ('sut' and 'xCT'), as well as heteroallelic offspring of these two strains ('xCT/sut') and their associated genetic backgrounds. Homozygous sut mutant males showed reduced spontaneous alternation in spontaneous alternation tasks as well as reduced movement in an open field maze, but xCT and xCT/sut strains did not show significant changes in these tasks compared to appropriate controls. Neither xCT nor sut mutants showed differences from controls in rotarod tests. Female behavioral phenotypes were independent of estrus cycle stage. To ensure that homozygous xCT, sut, and xCT/sut strains all represent protein null alleles, we measured whole brain xCT protein levels using immunoblots. xCT, sut and xCT/sut strains showed no detectable xCT protein expression, confirming them as null alleles. Previously published microdialysis experiments showed reduced striatal glutamate in xCT mutants. Using the same methods, we measured reduced interstitial glutamate levels in the striatum but not cerebellum of sut mutants. However, we detected no glutamate change in the striatum or cerebellum of sut/xCT mice. We detected no changes in whole brain EAAT-1, -2, or -3 expression. We conclude that the behavioral and chemical differences exist between slc7a11 mutant strains, but we were unable to definitively attribute any of these differences to loss of system xc-.
['McCullagh|Elizabeth A|EA|', 'Featherstone|David E|DE|']
D027182:Amino Acid Transport System y+ D000704:Analysis of Variance D000818:Animals D001921:Brain D004971:Estrus D005106:Exploratory Behavior D005260:Female D005786:Gene Expression Regulation D018698:Glutamic Acid D008297:Male D018782:Maze Learning D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D017551:Microdialysis D009043:Motor Activity D009154:Mutation D012737:Sex Factors D013997:Time Factors
System xc- xCT Extracellular glutamate Mouse behavior