[Study on differentially expressed gene of the liver of treble fatty metabolism genes mutant mice using cDNA microarray].
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.


CONCLUSIONS
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.
Jin
Xiao-lei
XL
College of Life Sciences, Siyuan Natural Medicine and Toxin Research Center, Zhejiang University, Hangzhou, Zhejiang, 310058 PR China.
Sun
Wen-xia
WX
Shi
Yu-ping
YP
Li
Jia-hui
JH
Chen
Han-min
HM
Pan
Jie
J
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011973:Receptors, LDL / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D011973:Receptors, LDL; D054411:Receptors, Leptin; D014280:Triglycerides; C515447:leptin receptor, mouse; D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase; D008049:Lipase; C075987:pancreatic lipase-related protein 1