FIGURE 10.
Expression of 24-hydroxylase gene and plasma 24(S)-hydroxycholesterol level in NPC. A, expression of 24-hydroxylase (Cyp46a1) gene in NPC mouse brain. The Cyp46a1 RNA level was determined by qPCR with total RNA extracted from the brain of Npc1+/− (+/−; n = 6), Npc1−/− (−/−; n = 6), and HPβCD-treated Npc1−/− (−/−; n = 6) mice. -Fold increase is expressed relative to transcript levels in Npc1+/− mice. B, expression of CYP46A1 gene in the cerebella of four NPC and four control subjects. Expression levels were determined by qPCR. -Fold change is relative to the average value of control subjects. Change above and below 1 (shown by the dotted line) represents the extent of up- and down-regulation, respectively. For both mouse and human qPCR studies, Gapdh was used as an internal control. Horizontal bars show the median values. C, 24(S)-HC levels in Npc1nih Npc1−/− (−/−) mice treated with saline or HPβCD compared with Npc1+/− (+/−). The plasma concentration of 24(S)-HC was determined by ELISA (see “Experimental Procedures”).