Altered sterol profile in the Cyp27a1−/−Cyp46a1−/− retina. A: A simplified scheme of cholesterol biosynthesis and initial steps of metabolism showing the sterols quantified in B–F. Quantification of lanosterol, lathosterol, and desmosterol (B); 24-OH and pregnenolone (C); cholesterol (D); cholestanol, a product of the bile acid intermediate 7α-hydroxy-4-cholesten-3-one (E); and 7-ketocholesterol (F). The results are the means of triplicate measurements of the pooled retinal samples (n = 40 per sex per genotype); error bars indicate SEM and represent technical variability. Because Cyp46a1−/− and Cyp27a1−/−Cyp46a1−/− mice were on a background (C57BL/6J;129S6/SvEv) different from that of Cyp27a1−/− mice (C57BL/6J), sterols in WT mice were measured in animals on two different background. Hatched bars indicate knockout mice while solid fill represents wild type. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. 7-Ketocholesterol, a product of cholesterol auto-oxidation; 24-OH, 24(S)-hydroxycholesterol; 27-COOH, 5-cholestenoic acid; 27-OH, 27-hydroxycholesterol; DKO, Cyp27a1−/−Cyp46a1−/− mice; SKO1, Cyp46a1−/− mice; SKO2, Cyp27a1−/− mice; WT, Cyp27a1+/+Cyp46a1+/+ mice.