Genetic variation in cholesterol absorption efficiency among inbred strains of mice

The initial study utilized the outbred Black Swiss, the inbred 129/SvEv and their hybrid mice to test for possible genetic difference in cholesterol absorption efficiency. Female mice (10-12 wk old) were fed a lipid test meal containing [3H]cholesterol and beta-[14C]sitosterol by stomach tube. The amount of [3H]cholesterol excreted in the feces was determined as nonabsorbed cholesterol and was normalized based on the recovery of the nonabsorbable beta-[14C]sitosterol. The Black Swiss mice absorbed significantly less cholesterol than the 129/SvEv mice within a 24-h period. Cholesterol absorption efficiency of the hybrid mice varied widely and did not segregate with either parental group. Differences in cholesterol absorption efficiency were also observed among six different inbred strains of mice fed either a basal low fat diet or a high fat/high cholesterol diet for 3 wk. Cholesterol absorption efficiency did not differ among DBA/2, C57BL/6, C3H/He, BALB/c and AKR/J mice under basal dietary conditions. However, cholesterol absorption was significantly lower in the DBA/2 mice than in C57BL/6 and C3H/He mice after mice were fed a high fat/high cholesterol diet. Cholesterol absorption by the C57L/J mice did not differ from that of C57BL/6, C3H/He, BALB/c and AKR/J mice under basal diet conditions, but was significantly lower when mice were fed a high fat/high cholesterol diet. Cholesterol absorption efficiency differed between DBA/2 and C57L/J mice under both dietary conditions. These results suggest that cholesterol absorption is controlled by multiple genetic factors.