Abstract 317: A Congenic Mouse Model for Carotid Intima-Media Thickening Demonstrates that Leukocyte Infiltration is a Genetically Regulated Trait
We demonstrated that inflammation and intima-media thickening (IMT) are increased in carotids exposed to low blood flow in the SJL/J (SJL) mouse strain compared to other strains. We identified three novel quantitative trait loci (QTLs) on chromosomes (chr) 2, 11, and 18 that control IMT in a genetic cross between C3HeB/FeJ (C3H/F) and SJL mice. Using a genetic backcross of C3H/FxSJL we measured inflammation in carotid IMT as a quantitative trait. Immunostaining for CD45+ (a pan-specific leukocyte marker) was performed on carotids from C3H/F, SJL, F1 and N2 progeny to measure leukocyte infiltration. A QTL for CD45+ cell infiltration was identified on chr11 (17cM, LOD=2.3). Interval mapping showed that the CD45+ locus accounted for 8% of the variation in the C3H/FxSJL backcross. Importantly, the CD45+ locus co-localized with our previously reported intima modifier 2 (Im2) locus. We created two Im2 congenic mice (C3H/F.SJL.11.1 and C3H/F.SJL.11.2) to define the contribution of chr11 to IMT. The C3H/F.SJL.11.1 congenic mouse showed elevated CD45+ staining in the vascular wall in response to low flow. Thus, the CD45+ trait partially explains the intima trait. This reveals a potential mechanistic relationship between leukocyte infiltration and IMT in response to decreased blood flow.
- © 2013 by American Heart Association, Inc.