Experiment
Previously identified QTL Bdt3 (bone density traits 3) at 67 cM on mouse Chromosome 6 is a pleiotropic locus associated with obesity, leptin levels, bone density, and VLDL/LDL levels. (C57BL/6J x DBA/2J)F2 animals homozygous for DBA/2J-derived alleles atBdt3 exhibit increased fat pad mass, plasma leptin, bone mineral density, and plasma VLDL/LDL cholesterol compared to F2 animals homozygous for C57BL/6J-derived alleles. F2 animals homozygous for DBA/2J-derived alleles at Alox5 (53.2 cM) also follow the same phenotypic pattern. In addition, B6.129S2-Alox5tm1Fun/J knockout animals also exhibit increased fat pads, plasma leptin and VLDL/LDL levels, and bone density compared to C57BL/6J.
The Bdt3 interval contains 331 genes. Expression QTL analysis of (C57BL/6JxDBA/2J)F2 liver RNA identified Alox5 as a strong candidate gene. The DBA/2J Alox5 gene sequence has 66 SNPs compared to C57BL/6J, which include 1 missense mutation (resulting in reduced Alox5 enzymatic activity) and 2 SNPs in the 3' untranslated region. Authors speculate Alox5 is in part responsible for the pleiotropic effects of Bdt3.