title: Genetic analysis of ligation-induced neointima formation in an F2 intercross of C57BL/6 and FVB/N inbred mouse strains.
abstract: OBJECTIVE
  Proliferation and migration of vascular smooth muscle cells (SMCs) are central for arterial diseases including atherosclerosis and restenosis. We hypothesized that the underlying mechanisms may be modeled by carotid ligation in mice. In FVB/N inbred mice, ligation leads to abundant neointima formation with proliferating media-derived SMCs, whereas in C57BL/6 mice hardly any neointima is formed. In the present study, we aimed to identify the chromosomal location of the causative gene variants in an F2 intercross between these two mouse strains.
  
  
  RESULTS
  The neointimal cross-sectional area was significantly different between FVB/N, C57BL/6 and F1 female mice 4 weeks after ligation. Carotid artery ligation and a genome scan using 800 informative SNP markers were then performed in 157 female F2 mice. Using quantitative trait loci (QTL) analysis, we identified suggestive, but no genome-wide significant, QTLs on chromosomes 7 and 12 for neointimal cross-sectional area and on chromosome 14 for media area. Further analysis of the cross revealed 4 QTLs for plasma cholesterol, which combined explained 69% of the variation among F2 mice.
  
  
  CONCLUSIONS
  We identified suggestive QTLs for neointima and media area after carotid ligation in an intercross of FVB/N and C57BL/6 mice, but none that reached genome-wide significance indicating a complex genetic architecture of the traits. Genome-wide significant QTLs for total cholesterol levels were identified on chromosomes 1, 3, 9, and 12.
authors: Department of Clinical Medicine, Aarhus University, and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Caroline
authors: C
authors: Östergren
authors: Department of Clinical Medicine, Aarhus University, and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Jeong
authors: J
authors: Shim
authors: Department of Clinical Medicine, Aarhus University, and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Jens Vinther
authors: JV
authors: Larsen
authors: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors: Lars Bo
authors: LB
authors: Nielsen
authors: Department of Clinical Medicine, Aarhus University, and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Jacob F
authors: JF
authors: Bentzon
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics*; D032389:Myocytes, Smooth Muscle; D058426:Neointima / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: D002784:Cholesterol