Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  10
• Reference
  J:179557 Wolfrum S, et al., The mouse atherosclerosis locus at chromosome 10 (Ath11) acts early in lesion formation with subcongenic strains delineating 2 narrowed regions. Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1583-90
• ID
  MGI:5824417

Genes

Gene
Ath11
Ath11a
Ath11b

Notes

• Experiment
  QTL mapping revealed an atherosclerosis susceptibility locus on mouse proximal chromosome 10 designated Ath11. The Chr 10 QTL suggested a dominant B6 allele lowered atherosclerotic lesion area, despite the fact that B6 was the atherosclerosis susceptible strain in that reciprocal intercross [(B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres)F2, J:76127].
  
  The objectives of this study were to assess how Ath11 affects lesion development and morphology, to determine aortic gene expression in congenics, and to narrow the congenic interval.
  
  Apoe -/- deficient mice on the B6 background (B6.129P2-Apoe^tm1Unc) and the FVB/N background (FVB.129P2-Apoe^tm1Bres) were used to confirm the Ath11 interval mapping from D10Mit49, 0.0 cM to D10Mit60, 21.9 cM, on Chr 10.
  
  To narrow the Ath11 interval 11 subcongenic strains containing a reduced portion of the original interval were generated by crossing B6.Apoe-/-Chr10^B6/FVB heterozygotes with B6.Apoe-/- littermates. Recombinants missing part of the original FVB interval were identified and bred to FVB.Apoe-/- mice to generate littermates that were either F1.Apoe-/-Chr10^FVB/FVB or F1.Apoe-/-Chr10^B6/FVB. The boundaries of each subcongenic strain were fine mapped by sequencing regions containing polymorphic SNPs between B6 and FVB. Aortic root lesion size area was assessed in 957 mice.
  
  F1.Apoe-/- mice that were homozygous B6, heterozygous B6/FVB and homozygous FVB in the congenic interval were weaned at 4 weeks of age onto a semi-synthetic AIN76a diet containing 0.02% cholesterol and sacrificed for atherosclerotic lesion quantification at 6, 12, 16, 20 and 24 weeks of age. In general, atherosclerotic lesion areas did not differ at any time point between the B6 homozygous and the heterozygous mice. In contrast, at each time point atherosclerotic lesion area was increased in FVB homozygotes.
  
  QTL Ath11a (atherosclerosis 11a) was identified as a B6 atheroprotective gene, detectable only in female mice, identified in region 10a defined by subcongenics D (0-rs50156646) and G (0-rs4228112), which showed decreased atherosclerosis lesion area in heterozygotes vs FVB homozygous female mice and subcongenics L (rs29349441-rs50156646) and R (rs29349441-rs13480506), which showed equal lesion area in heterozygotes vs FVB homozygotes in both genders. This placed the culprit gene in the 10a region between 0 and rs29349441, a region spanning 0 to 7.3 Mb and containing 21 genes including Esr1, Oprm1, Myct1, Syne1 and 9230019H11Rik [Table 2].
  
  QTL Ath11b (atherosclerosis 11b), another atheroprotective gene, detectable in both genders, mapped to region 10b defined by subcongenic strain I (JMR2001-rs52653661), which showed decreased atherosclerosis lesion area in heterozygotes vs FVB homozygous mice of both genders. The culprit gene in the 10b region maps in a 1.8 Mb interval from 20.1 to 21.9 Mb containing 7 genes: Pde7b, Ahi1, Myb, Hbs1l, Aldh8a1, Sgk1 and Reat1 [Table 2].
  
  Total and HDL cholesterol levels were determined for all subcongenic strains and there were no significant differences between heterozygotes and FVB homozygotes, male or female mice.