Effects of genetic disruption of the apoA-I gene (a) or probucol treatment (b and c) on plasma lipoprotein profiles of wild-type and SR-BI KO mice. Plasma lipoproteins were separated by size-exclusion chromatography (Superose 6-FPLC), and total cholesterol was measured for each fraction (expressed as milligrams per deciliter of plasma). Approximate elution positions of VLDL, IDL/LDL, and HDL are indicated as described previously (19). Lipoprotein-cholesterol profiles of (a) wild-type (dashed line, pooled plasma from four mice); SR-BI KO mice (open circles, pooled plasma from seven mice); apoA-I KO mice (open triangles, pooled plasma from three mice); and SR-BI/apoA-I double-KO mice (filled triangles; average of three chromatograms from three mice); (b) wild-type mice fed first with normal chow (open squares, pooled plasma from four mice, same as dashes in a); then with 0.5% probucol-enriched chow for 11 days (filled squares, pooled plasma from four mice); and (c) SR-BI KO mice fed first with normal chow (open circles, pooled plasma from seven mice, same as in a); and then with 0.5% probucol-enriched chow for 25 days (filled circles, pooled plasma from seven mice). The average plasma total cholesterol levels (± SEM) were: wild-type, 103.4 ± 3.8 mg/dl (n = 7); SR-BI KO, 211.5 ± 6.2 mg/dl (n = 13); apoA-I KO, 25 ± 1.2 mg/dl (n = 3); SR-BI/apoA-I KO, 105.3 ± 19.2 mg/dl (n = 3); probucol-fed wild-type, 33.6 ± 3.4 mg/dl (n = 9); probucol-fed SR-BI KO, 107.8 ± 6.3 mg/dl (n = 14). All total cholesterol differences greater than 10 mg/dl were statistically significant (P < 0.05).