Role of ABCG1 in plaque regression

Mechanistic studies on the roles of individual genes in plaque regression have been restricted due to the limitations of current regression models. In the REVERSA mouse, a humanised mouse model of atherosclerosis, high lipid levels can be normalised by an inducible deletion of a conditional allele, leading to regression of established lesions. However, this model has had limited utility, because the 4 independently-segregating alleles effectively prevents further cross-breeding to introduce another allele. In this project we used genome-editing in the REVERSA mouse, to enable, for the first time, the investigation of the specific role of reverse cholesterol transport in plaque regression. We have used this model to explore novel pathways and cellular mechanisms that mediate atherosclerotic plaque regression.