on February 26, 2009
Published online before print February 26, 2009, doi: 10.1161/ATVBAHA.108.179408
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Submitted on October 21, 2008
Accepted on February 2, 2009
Novel Strategy Using F1-Congenic Mice for Validation of QTLs. Studies at the Proximal Chromosome 10 Atherosclerosis Susceptibility Locus
Daniel Teupser ;
From the Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York.
* To whom correspondence should be addressed. E-mail: breslow{at}rockefeller.edu.
Objective—We have previously identified a quantitative trait locus (QTL) for atherosclerosis susceptibility on proximal chromosome 10 (Chr10) (Ath11) in independent crosses of FVB and C57BL/6 (B6) mice on the apolipoprotein E (ApoE-/-) and LDL receptor (LDLR-/-) deficient backgrounds. The aims of the current study were to (1) test a novel strategy for validating QTLs using interval-specific congenic strains that were heterozygous (F1) across the genome, (2) validate the Chr10 QTL, and (3) to assess whether the phenotype is transferable by bone marrow transplantation.
Methods and Results—We generated Chr10 (0 to 21 cM) interval-specific mice on the F1.ApoE-/- background by crossing congenic FVB.ApoE-/-Chr10B6/FVB with B6.ApoE-/-, and B6.ApoE-/-Chr10B6/FVB with FVB.ApoE-/- mice. Lesion size was significantly larger in the resultant F1.ApoE-/-Chr10FVB/FVB mice compared to F1.ApoE-/- Chr10B6/FVB and F1.ApoE-/-Chr10B6/B6 mice, validating the Chr10 QTL. The effect of the congenic interval was more robust on the F1.ApoE-/- than on the FVB.ApoE-/- and B6.ApoE-/- backgrounds. Bone marrow transplantation in congenic mice showed that the effect of the proximal Chr10 interval was not transferable by bone marrow–derived cells.
Conclusions—A novel strategy of congenic strains on an F1 background proved useful to validate an atherosclerosis susceptibility QTL on mouse proximal Chr10.
Key words: atherosclerosis • congenic mice • chromosome 10 • transplantation