FIGURE 2.

Plasma cathepsin S levels are elevated in Npc1^nih and Npc1^nmf164 mice and reduced after cyclodextrin treatment. A, weight as a function of age for Npc1^nih male and female mice. Homozygous mutant Npc1^nih (Npc1^−/−) mice begin weight loss at 49–56 days followed by further decreases and death at 77–84 days. B, elevated cathepsin S detected in plasma of Npc1^nih Npc1^−/− mice as determined by ELISA (“Experimental Procedures”). C, weight as a function of age of Npc1^nmf male and female mice. Homozygous mutant Npc1^nmf (Npc1^−/−) mice lose weight from 84–91 days onward followed by further decreases and death at 119–126 days. D, elevated cathepsin S level in plasma of Npc1^nmf Npc1^−/− mice. E, cathepsin S levels in Npc1^nih Npc1^−/− (−/−) mice treated with saline or HPβCD compared with Npc1^+/− (+/−). F, cathepsin S levels in Npc1^nmf Npc1^−/− (−/−) mice treated with saline or HPβCD compared with Npc1^+/− (+/−). In B, D, E, and F, blood plasma was sampled at the indicated time points. -Fold change in cathepsin S is expressed relative to average levels of activity in Npc1^+/− mouse plasma. The data represent mean triplicate values ±S.D. (error bars). Median values are shown by horizontal lines. Statistical significance was determined using Student's t test. *, p < 0.0001 in B, p < 0.05 in D, and p < 0.00001 in E. NS indicates not significant. gm, grams; AU, arbitrary units.