Differential mRNA expression of seven genes involved in cholesterol metabolism and transport in the liver of atherosclerosis-susceptible and -resistant Japanese quail strains.
BACKGROUND
Two atherosclerosis-susceptible and -resistant Japanese quail (Coturnix japonica) strains obtained by divergent selection are commonly used as models to study atherosclerosis, but no genetic characterization of their phenotypic differences has been reported so far. Our objective was to examine possible differences in the expression of genes involved in cholesterol metabolism and transport in the liver between these two strains and to evaluate the value of this model to analyze the gene system affecting cholesterol metabolism and transport.


METHODS
A factorial study with both strains (atherosclerosis-susceptible versus atherosclerosis-resistant) and two diets (control versus cholesterol) was carried out. The mRNA concentrations of four genes involved in cholesterol biosynthesis (HMGCR, FDFT1, SQLE and DHCR7) and three genes in cholesterol transport (ABCG5, ABCG8 and APOA1) were assayed using real-time quantitative PCR. Plasma lipids were also assayed.


RESULTS
Expression of ABCG5 (control diet) and ABCG8 (regardless of dietary treatment) and expression of HMGCR, FDFT1 and SQLE (regardless of dietary treatment) were significantly higher in the atherosclerosis-resistant than in the atherosclerosis-susceptible strain. Plasma triglyceride and LDL levels, and LDL/HDL ratio were significantly higher in the atherosclerosis-susceptible than in the atherosclerosis-resistant strain fed the cholesterol diet. In the atherosclerosis-susceptible strain, ABCG5 expression regressed significantly and positively on plasma LDL level, whereas DHCR7 and SQLE expression regressed significantly and negatively on plasma triglyceride level.


CONCLUSIONS
Our results provide support for the hypothesis that the atherosclerosis-resistant strain metabolizes and excretes cholesterol faster than the atherosclerosis-susceptible strain. We have also demonstrated that these quail strains are a useful model to study cholesterol metabolism and transport in relation with atherosclerosis.
Avian Research Centre, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada.
Xinrui
X
Li
Patricia
P
Schulte
David V
DV
Godin
Kimberly M
KM
Cheng
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics*; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003370:Coturnix / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D004032:Diet; D060467:Disease Resistance / Q000235:genetics*; D004198:Disease Susceptibility / Q000097:blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012044:Regression Analysis; D015398:Signal Transduction / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; D008798:Mevalonic Acid