PMID- 17916774
OWN - NLM
STAT- MEDLINE
DCOM- 20071211
LR  - 20071121
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 27
IP  - 12
DP  - 2007 Dec
TI  - Mapping, genetic isolation, and characterization of genetic loci that determine 
      resistance to atherosclerosis in C3H mice.
PG  - 2671-6
AB  - OBJECTIVE: C3H/HeJ (C3H) mice are extremely resistant to atherosclerosis. To 
      identify the genetic factors involved in lesion initiation, we studied a cross 
      between C3H and the susceptible strain C57BL/6J (B6) on a hyperlipidemic 
      (apolipoprotein E-null) background. METHODS AND RESULTS: Whereas a previous cross 
      in mice fed a Western diet for 16 weeks revealed a very complex inheritance 
      pattern with many significant lesion QTLs, the present cross, on a chow diet, 
      revealed a single major locus on chromosome 9 (lod=5.0, Ath29*), and a suggestive 
      locus on chromosome 4 (lod=2.6, Ath8). QTLs for plasma HDL, total cholesterol, 
      and triglyceride levels were found on chromosome 1 over the ApoA2 gene. Neither 
      of the lesion QTLs were associated with differences in plasma lipid levels or 
      other systemic risk factors, consistent with the concept that genetic factors 
      affecting cellular functions of the vessel wall are important determinants of 
      atherosclerosis susceptibility. We generated a congenic strain for Ath29 and 
      confirmed its contribution to lesion development. Toll-like receptor 4 (Tlr4), 
      the lipopolysaccharide (LPS) receptor, is located in the Ath8 region and is known 
      to be defective in C3H/HeJ mice. We constructed a congenic strain carrying a 
      normal Tlr4 gene on the C3H Apoe-null background and found that the defective 
      Tlr4 does not contribute significantly to lesion resistance during early lesion 
      development. CONCLUSIONS: We identified one major QTL on chromosome 9, Ath29, for 
      early lesion development in the BXH ApoE(-/-) cross fed on a chow diet and 
      confirmed its contribution in congenic mice. We have also determined that Tlr4 on 
      the C3H ApoE(-/-) background does not contribute to early lesion development. 
      *Ath29 is referred to as Ath22 in Su et al 2006.
FAU - Wang, Susanna S
AU  - Wang SS
AD  - UCLA School of Medicine, Dept. of Human Genetics, Box 95167, University of 
      California at Los Angeles, Los Angeles, CA 90095-1679, USA.
FAU - Shi, Weibin
AU  - Shi W
FAU - Wang, Xuping
AU  - Wang X
FAU - Velky, Leandra
AU  - Velky L
FAU - Greenlee, Sarah
AU  - Greenlee S
FAU - Wang, Min T
AU  - Wang MT
FAU - Drake, Thomas A
AU  - Drake TA
FAU - Lusis, Aldons J
AU  - Lusis AJ
LA  - eng
GR  - HL28481/HL/NHLBI NIH HHS/United States
GR  - HL30568/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071004
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Apolipoproteins E)
RN  - 0 (Dietary Fats)
RN  - 0 (Lipids)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/deficiency/genetics/*metabolism
MH  - Atherosclerosis/*genetics/metabolism/pathology
MH  - *Chromosome Mapping
MH  - Crosses, Genetic
MH  - Dietary Fats/administration & dosage
MH  - Disease Models, Animal
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Lipids/blood
MH  - Mice
MH  - Mice, Congenic
MH  - Mice, Inbred C3H/*genetics
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mutation
MH  - *Quantitative Trait Loci
MH  - Risk Factors
MH  - Toll-Like Receptor 4/genetics
EDAT- 2007/10/06 09:00
MHDA- 2007/12/12 09:00
CRDT- 2007/10/06 09:00
PHST- 2007/10/06 09:00 [pubmed]
PHST- 2007/12/12 09:00 [medline]
PHST- 2007/10/06 09:00 [entrez]
AID - ATVBAHA.107.148106 [pii]
AID - 10.1161/ATVBAHA.107.148106 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2671-6. doi: 
      10.1161/ATVBAHA.107.148106. Epub 2007 Oct 4.