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- W2079254251 abstract "Objective— We demonstrated that inflammatory cells and intima–media thickening are increased in carotids exposed to low-blood flow in the SJL/J (SJL) strain compared with other mouse strains. We hypothesized that the extent of inflammation associated with intima–media thickening is a genetically regulated trait. Approach and Results— We performed a whole genome approach to measure leukocyte infiltration in the carotid intima as a quantitative trait in a genetic cross between C3HeB/FeJ (C3H/F) and SJL mice. Immunostaining for CD45 + (a pan-specific leukocyte marker) was performed on carotids from C3H/F, SJL, F1, and N2 progeny to measure leukocyte infiltration. We identified a nearly significant quantitative trait locus for CD45 + on chromosome (chr) 11 (17 cM, LOD=2.3; significance was considered at threshold P =0.05). Interval mapping showed that the CD45 + locus on chr 11 accounted for 8% of the variation in the logarithm of odds backcross. Importantly, the CD45 + locus colocalized with the intima-modifier 2 ( Im 2) locus, which controls 17% of intima variation. We created 2 Im 2 congenic lines of mice (C3H/F.SJL.11.1 and C3H/F.SJL.11.2) to better understand the regulation of intima–media thickening by the chr 11 locus. The C3H/F.SJL.11.1 congenic mouse showed ≈30% of the SJL trait, confirming that CD45 + cell infiltration contributed to the intima trait. Conclusions— We discovered a novel locus on chr 11 that controls leukocyte infiltration in the carotid. Importantly, this locus overlaps with our previously published Im 2 locus on chr 11. Our study reveals a potential mechanistic relationship between leukocyte infiltration and intima–media thickening in response to decreased blood flow." @default.
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- W2079254251 date "2013-05-01" @default.
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- W2079254251 title "Identification of a Genetic Locus on Chromosome 11 That Regulates Leukocyte Infiltration in Mouse Carotid Artery" @default.
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- W2079254251 doi "https://doi.org/10.1161/atvbaha.112.301129" @default.
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