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Journal of Lipid Research, Vol 36, 1522-1532, Copyright © 1995 by Lipid Research, Inc.
EA Kirk, GL Moe, MT Caldwell, JA Lernmark, DL Wilson and RC LeBoeuf
A concept proposed by Berg (Berg, K. 1989. Arteriosclerosis. 9: I-50-I- 58)
is that a combination of level and variability genes determine an
individual's overall plasma lipid levels and atherosclerotic risk. Our goal
was to determine which inbred mouse strains could be used to identify
candidate level and variability genes controlling lipid levels and
atherosclerosis susceptibility. Nine common inbred mouse strains were
examined for responsiveness with respect to plasma lipoprotein and tissue
lipid levels upon feeding diets rich in cholesterol and fat. Marked
quantitative variations were observed in plasma cholesterol and
triglyceride levels among mice fed rodent chow and the high fat test diets.
Mice of strains DBA/2 and AKR appeared to be hyporesponsive to diets
containing high levels of fat and cholesterol as compared to rodent chow.
In contrast, several strains were primarily hyperresponsive to either
dietary fat or cholesterol, or both ingredients. Determination of
cholesterol absorption for selected strains fed test diets suggested that
decreased cholesterol absorption, in part, contributes to
hyporesponsiveness as seen in DBA/2 mice. Levels of mRNA for cholesterol 7
alpha-hydroxylase were estimated and shown to vary markedly among strains.
An inverse correlation was seen among strains between cholesterol 7
alpha-hydroxylase mRNA, and plasma and hepatic cholesterol levels for some
diets. Thus, genes controlling cholesterol absorption and bile acid
synthesis are candidates for further study as level and variability genes
affecting plasma cholesterol levels. Overall, inbred mouse strains will
prove useful for identifying genes controlling level and variability
traits.
ARTICLES
Hyper- and hypo-responsiveness to dietary fat and cholesterol among inbred mice: searching for level and variability genes
Department of Medicine, University of Washington, Seattle 98195, USA.
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