(A) and (B) effects of UDCA bile acid supplementation on the activity of CYP450 catalysed reactions in the Npc1 mouse model of plus or minus 0.5% ursodeoxycholic acid (UDCA, w/w) measured at (A) 6 weeks and (B) 9 weeks of age, shown as a function of percent of age-matched control littermates. Methoxyresorufin-O-dealkylation (MROD); ethoxyresorufin-O-dealkylation (EROD); pentoxyresorufin-O-dealkylation (PROD); benzoxyresorufin-O-dealkylation (BROD). Data are presented as mean ± SEM, n = 6 (3 males and 3 females), * p—value < 0.05, ** p—value < 0.01, *** p—value < 0.001, **** p—value < 0.0001 calculated using an unpaired nonparametric test Mann-Whitney test. (C) Relative protein quantitation of Cyp3a isolated from liver of 6-week old male mice found a significant decrease in Npc1+/- and Npc1-/- untreated mice compared Npc1+/+ untreated mice. UDCA treatment restored Npc1-/- Cyp3a levels to that of Npc1+/+ mice while have no effect on the Npc1+/- or Npc1+/+ Cyp3a values. (D) Relative protein quantitation of Cyp1a2 isolated from liver of 6-week old male mice found a significant decrease in Npc1+/- and Npc1-/- untreated mice compared Npc1+/+ untreated mice. UDCA treatment restored Npc1-/- Cyp1a2 levels to that of Npc1+/+ mice while decreasing the levels for Npc1+/- and Npc1+/+ Cyp1a2 values. Data are presented as mean ± SD, n = 3. * p—value < 0.05, ** p—value < 0.01, *** p—value < 0.001 calculated using two-tailed, unpaired t test. (F) Representative western blot analysis of Cyp3a and Cyp1a2 in the mouse model of Npc1 plus or minus UDCA treatment.