QTL mapping for genetic determinants of lipoprotein cholesterol levels in combined crosses of inbred mouse strains

Henning Wittenburg*, Malcolm A. Lyons, Renhua Li, Ulrike Kurtz, Xiaosong Wang, Joachim Mössner, Gary A. Churchill, Martin C. Carey, Beverly Paigen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


To identify additional loci that influence lipoprotein cholesterol levels, we performed quantitative trait locus (QTL) mapping in offspring of PERA/EiJXI/LnJ and PERA/EiJXDBA/2J intercrosses and in a combined data set from both crosses after 8 weeks of consumption of a high fat-diet. Most QTLs identified were concordant with homologous chromosomal regions that were associated with lipoprotein levels in human studies. We detected significant new loci for HDL cholesterol levels on chromosome (Chr) 5 (Hdlq34) and for non-HDL cholesterol levels on Chrs 15 (Nhdlq9) and 16 (Nhdlq10). In addition, the analysis of combined data sets identified a QTL for HDL cholesterol on Chr 17 that was shared between both crosses; lower HDL cholesterol levels were conferred by strain PERA. This QTL colocalized with a shared QTL for cholesterol gallstone formation detected in the same crosses. Haplotype analysis narrowed this QTL, and sequencing of the candidate genes Abcg5 and Abcg8 confirmed shared alleles in strains I/LnJ and DBA/2J that differed from the alleles in strain PERA/EiJ. In conclusion, our analysis furthers the knowledge of genetic determinants of lipoprotein cholesterol levels in inbred mice and substantiates the hypothesis that polymorphisms of Abcg5/Abcg8 contribute to individual variation in both plasma HDL cholesterol levels and susceptibility to cholesterol gallstone formation.

Original languageEnglish
Pages (from-to)1780-1790
Number of pages11
JournalJournal of Lipid Research
Issue number8
StatePublished - 2006
Externally publishedYes


  • Abca1
  • Abcg5
  • Abcg8
  • High density lipoprotein
  • Low density lipoprotein
  • Quantitative trait locus


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