Original Article Differences in Expression of Cholesterol 7α-Hydroxylase between PHHC and Wistar Rats

Abstract. PHHC rats represent a suitable experi-mental model of polygenic hypercholesterolemia. It has been found that its metabolic defect is not related to alimentary cholesterol absorption and LDL clear-ance. We have tested possible changes in cholesterol clearance from the liver to bile acids by analysis of the expression of the cholesterol 7α-hydroxylase (cyp7A1) gene in PHHC (N = 20) and Wistar (con-trols) (N = 19) male rats. The animals were fed stand-ard laboratory diet (CD) or control diet containing 5 % fat and 2 % cholesterol (HCD) for two weeks. SSCP and RT-PCR were used for mutation analysis and study of gene expression, respectively. Although the basal cholesterolemia in PHHC was similar to controls (1.80 ± 0.48 and 1.52 ± 0.39 mmol/l, respec-tively), it rose in rats fed on HCD to 9.81 ± 1.65 mmol/l in PHHC rats and only to 2.19 ± 0.41 mmol/l in con-trols. Similarly to the basal cholesterol concentra-tion, the gene expression of cyp7A1 in the liver of rats on CD was the same in both compared groups on the control diet. In controls on HCD, cyp7A1 gene ex-pression increased almost 4-fold immediately on the first day and achieved up to ~ 20-multiple basal ex-pression in the end of the feeding period. Compared to the controls, after switching to HCD the cyp7A1 gene expression in PHHC rats did not change dra-matically. These results suggest that the cyp7A1 gene plays an important role in development of hypercho-lesterolemia in PHHC rats