Abstract
The concentration of free and esterified cholesterol and the activities of the cholesterol esterifying enzyme and cholesterol ester hydrolases in brains from Jimpy and Quaking mice and their normal littermates were determined. In Quaking affected mice these brain components did not differ significantly from those in brains of normal littermates. In the Jimpy affected mouse brain, however, the concentration of free cholesterol was reduced and the esterified cholesterol was increased. The increase in esterified cholesterol was accompanied by higher activity of cholesterol esterifying enzyme and a significant reduction in activity of hydrolases. In the absence of exogenous fatty acids, cholesterol esterification by cell-free preparations of brain from Jimpy affected mice was also significantly higher than the normal littermates. These data indicate that an increase in cholesterol ester concentrations in Jimpy affected brain may result either from an increase in esterification due to an increase in the availability of free fatty acid as substrate, or from deficiency in the activity of the hydrolases. In addition, the data indicate that in Jimpy mutants there is a significant reduction in brain cholesterol content, whereas in Quaking mutants the sterol content of developing brain is not significantly affected. This suggests that during brain development sterol synthesis in brain is reduced in Jimpy but not in Quaking mutants.
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