Formation and Metabolism of Oxysterols and Cholestenoic acids Found in the Mouse Circulation: Lessons Learnt from Deuterium-Enrichment Experiments and the CYP46A1 Transgenic Mouse

In this study by observing the metabolism of deuterium-labelled cholesterol in the pdgfbret/ret mouse, a mouse model with increased vascular permeability in brain, and by studying the sterol content of plasma from the CYP46A1 transgenic mouse overexpressing the human cholesterol 24S-hydroxylase enzyme we have been able to identify a number of minor cholesterol metabolites found in the circulation, make approximate-quantitative measurements and postulate pathways for their formation. These “proof of principle” data may have relevance when using mouse models to mimic human disease and in respect of the increasing possibility of treating human neurodegenerative diseases with pharmaceuticals designed to enhance the activity of CYP46A1 or by adeno-associated virus delivery of CYP46A1.
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research