Objective: To study the gene expression profile of liver of young apoE(-/-)/LDLR(-/-)/Lepr(db/db) treble genes mutant mice and disclose its relationship to hyperlipidemia and the following atherosclerotic lesion.
Methods: The gene expression profile was investigated using cDNA microarray technique; the plasma total cholesterol(TC) and triglyceride(TG) levels were analyzed by COD-PAP and GPO-PAP method. And morphological observations of the aorta were made.
Results: Among the 4000 target genes, 92 genes were up-regulated and 105 genes were down-regulated in the treble genes mutants, compared with wild type control. Among the differentially expressed lipid metabolism related genes, cholesterol synthesis gene coding for farnesyl diphosphate farnesyl transferase was down-regulated, while triglyceride metabolism gene e.g. pancreatic lipase related protein 1 gene (Pnliprp1) was up-regulated. Expression profile of carbohydrate, cell skeleton and immune related genes were also altered. On the other hand, in the plasma from the treble genes mutant mice at 5 weeks of age, hyperlipidemia was found to be combined with atheroslerotic lesion. All these biochemical and pathological changes were aggravated following aging.
Conclusion: The data suggested that the multiple genes mutations, especially those involved in lipid metabolism, were contributing to the alteration of liver gene expression profile that might lead to hyperlipidemia and atherosclerotic lesion in the young apoE(-/-)/LDLR(-/-)/Lepr(db/db) mutants.