UBC Theses and Dissertations
An investigation of the atherosclerosis susceptibility difference between two strains of Japanese quail based on gene expression profiling Li, Xinrui
Atherosclerosis is influenced by a large number of genetic and environmental factors. There is an urgent need for more research exploring the atherogenic process, so that more effective therapeutic approaches can be devised. Japanese quail (Coturnix japonica) form very complex vascular lesions similar to those in humans. The atherosclerosis-susceptible (SUS) and resistant (RES) quail are particularly useful models. They were developed by divergent selection but there has been no genetic characterization of the strains. Genetic characterization of the differences between these two strains would not only improve the utility of this model, but also enable researchers to make more meaningful interpretation of the data generated using this model. This thesis research was conducted primarily to examine the differences between these two strains in terms of the expression of genes related to atherogenesis, but to also gain insights into the role cholesterol metabolism plays in atherosclerosis. The first study investigated the expression of cholesterol synthesis genes HMGCR, FDFT1, SQLE, DHCR7 and cholesterol transporter genes ABCG5, ABCG8 and APOA1 in the liver. The results showed that HMGCR, FDFT1 and SQLE had significantly higher expression in the RES than in SUS. RES showed significantly higher expression of ABCG8 than did SUS. RES had significantly higher expression of ABCG5 than did SUS on a regular diet. Both strains had significantly increased APOA1 expression when challenged by dietary cholesterol. These results provided evidence to support the hypothesis that the RES were more resistant to atherosclerosis partly because “they metabolized and excreted cholesterol faster than SUS”. In the second study, the cDNA-AFLP technique was used to indentify gene expression differences between the SUS and the RES quail. AFLP reactions using Mse and EcoR primer combinations on liver tissues found one out of 1150 fragments being differentially expressed in the liver while there were no strain-related differences detected in the spleen. The results support the hypothesis that the divergent selection used to develop these two strains did not drastically altered their genotype. However, it is not possible to draw definitive conclusions because the small number of primer pairs used only covered 9% of the quail genome.
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