Ataxia with vitamin E deficiency is caused by mutations in α-tocopherol transfer protein (α-TTP) gene and it can be experimentally generated in mice by α-TTP gene inactivation (α-TTP-KO). This study compared α-tocopherol (α-T) concentrations of five brain regions and of four peripheral organs from 5 months old, male and female, wild-type (WT) and α-TTP-KO mice. All brain regions of female WT mice contained significantly higher α-T than those from WT males. α-T concentration in the cerebellum was significantly lower than that in other brain regions of WT mice. These sex and regional differences in brain α-T concentrations do not appear to be determined by α-TTP expression which was undetectable in all brain regions. All the brain regions of α-TTP-KO mice were severely depleted in α-T. The concentration of another endogenous antioxidant, total glutathione, was unaffected by gender but was decreased slightly but significantly in most brain regions of α-TTP-KO mice. The results show that both gender and the hepatic α-TTP, but not brain α-TTP gene expression are important in determining α-T concentrations within the brain. Interestingly, functional abnormality (ataxia) develops only very late in α-TTP-KO mice in spite of the severe α-tocopherol deficiency in brain starting at an early age.

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