Mice lacking alpha-tocopherol transfer protein gene have severe alpha-tocopherol deficiency in multiple regions of the central nervous system.
Ataxia with vitamin E deficiency is caused by mutations in alpha-tocopherol transfer protein (alpha-TTP) gene and it can be experimentally generated in mice by alpha-TTP gene inactivation (alpha-TTP-KO). This study compared alpha-tocopherol (alpha-T) concentrations of five brain regions and of four peripheral organs from 5 months old, male and female, wild-type (WT) and alpha-TTP-KO mice. All brain regions of female WT mice contained significantly higher alpha-T than those from WT males. alpha-T concentration in the cerebellum was significantly lower than that in other brain regions of WT mice. These sex and regional differences in brain alpha-T concentrations do not appear to be determined by alpha-TTP expression which was undetectable in all brain regions. All the brain regions of alpha-TTP-KO mice were severely depleted in alpha-T. The concentration of another endogenous antioxidant, total glutathione, was unaffected by gender but was decreased slightly but significantly in most brain regions of alpha-TTP-KO mice. The results show that both gender and the hepatic alpha-TTP, but not brain alpha-TTP gene expression are important in determining alpha-T concentrations within the brain. Interestingly, functional abnormality (ataxia) develops only very late in alpha-TTP-KO mice in spite of the severe alpha-tocopherol deficiency in the brain starting at an early age.
Gohil
Kishorchandra
K
Department of Internal Medicine, Genome and Biomedical Sciences Facility, University of California, Davis, CA 95616, USA. kgohil@ucdavis.edu
Oommen
Saji
S
Quach
Hung T
HT
Vasu
Vihas T
VT
Aung
Hnin Hnin
HH
Schock
Bettina
B
Cross
Carroll E
CE
Vatassery
Govind T
GT
D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001931:Brain Mapping; D002352:Carrier Proteins / Q000235:genetics*; D002490:Central Nervous System / Q000033:anatomy & histology / Q000378:metabolism* / Q000503:physiopathology; D002531:Cerebellum / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005526:Food, Formulated; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012727:Sex Characteristics; D024502:alpha-Tocopherol / Q000378:metabolism*
D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein; D005978:Glutathione; D024502:alpha-Tocopherol