Modulation and compensation of the mRNA expression of energy related transporters in the brain of glucose transporter 1-deficient mice.
Facilitative glucose transporter 1 (GLUT1) is the molecule responsible for the entry of glucose into the brain, and its mutation is known as GLUT1 deficiency syndrome (GLUT1DS) in humans. To clarify the effect of GLUT1 gene deficiency, we have produced GLUT1-deficient mice, and investigated the developmental expression of GLUT1, monocarboxylate transporter 1 (MCT1) and MCT2 in the brains of these mice. Since the homozygotes were found to be embryonically lethal and the heterozygotes exhibited no abnormalities, GLUT1deficiency was examined using heterozygote mice. GLUT1 deficiency did not significantly affect the mRNA levels of GLUT1 at P0, P7 and in adults, or the levels of MCTs at P7, P14 and in adults. The GLUT1 level at P14 was reduced by 46.9%, although this was not statistically significant. The MCTs levels at P0 were increased about 2.0-fold in the deficient mice compared with the wild type. Furthermore, at P0, GLUT1 mRNA levels in wild type females were 1.91-fold higher than in wild type males. These results suggest that GLUT1 deficiency affects GLUT1 mRNA expression in the infant brain, and that of MCT1 and MCT2 in the neonatal brain. Furthermore, a compensatory effect of GLUT1 expression was observed in the brain of adult deficient mice. These effects of GLUT1 deficiency in the brain provide a molecular basis to assist in our understanding of the symptoms of GLUT1DS.
Ohtsuki
Sumio
S
Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
Kikkawa
Tazuru
T
Hori
Satoko
S
Terasaki
Tetsuya
T
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger