title: Identification of a genetic locus on chromosome 11 that regulates leukocyte infiltration in mouse carotid artery.
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.
  
  
  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 (Im2) locus, which controls 17% of intima variation. We created 2 Im2 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 Im2 locus on chr 11. Our study reveals a potential mechanistic relationship between leukocyte infiltration and intima-media thickening in response to decreased blood flow.
authors: University of Rochester, Aab Cardiovascular Research Institute, 601 Elmwood Ave, Box CVRI, Rochester, NY 14642, USA. Elaine_Smolock@urmc.rochester.edu
authors: Elaine M
authors: EM
authors: Smolock
authors: Dietrich E
authors: DE
authors: Machleder
authors: Vyacheslav A
authors: VA
authors: Korshunov
authors: Bradford C
authors: BC
authors: Berk
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D002465:Cell Movement; D033481:Chromosomes, Mammalian; D005260:Female; D017493:Leukocyte Common Antigens / Q000032:analysis; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D040641:Quantitative Trait Loci; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D000199:Actins; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse