Bdt3^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Bdt3^DBA/2J
• Name: bone density traits 3; DBA/2J
• MGI ID: MGI:2156404
• QTL: Bdt3 Location: unknown Genetic Position: Chr6, cM position of peak correlated region/allele: 63.63 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased fat pad mass, bone mineral density, plasma leptin, and plasma VLDL/LDL compared to C57BL/6J (J:104825)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

3 anatomical structure(s)

Notes

Candidate Genes

J:104825

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-Alox5^tm1Fun/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.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:69682

Genome scan at an average marker spacing of 13 cM was performed on female animals from a (C57BL/6J x DBA/2J)F2 intercross to identify QTLs associated with bone density and bone density related traits. Animals were placed on a 16 week atherogenic diet at 12 months of age. QTLs were identified on mouse Chromosome 2 spanning 90 cM - 130 cM (Bdt1, LOD = 5.65 at D2Mit413), mouse Chromosome 3 spanning 40 cM - 70 cM (Bdt2, LOD = 8.09 at D3Mit14), mouse Chromosome 6 spanning 60 cM - 85 cM (Bdt3, LOD = 6.4 at D6Mit198), mouse Chromosome 7 spanning 0 cM - 50 cM (Bdt4, LOD = 8.28 at D7Mit80), and mouse Chromosome 15 spanning 0 cM - 30 cM (Bdt5, LOD = 6.13 at D15Mit13) and spanning 20 cM - 50 cM (Bdt6, LOD = 7.73 at D15Mit206). ANOVA analysis detected interaction between Bdt3 on Chromosome 6 and Bdt5 on Chromosome 15. Bdt1, Bdt2, and Bdt3 colocalize with QTLs for nonbone traits and may indicate pleiotropic effects at these loci. Further investigation concluded Bdt2 is distinct from colocalizing loci for body length and HDL cholesterol, but did not rule out pleiotropy at Bdt1 for adipose mass and HDL cholesterol and at Bdt2 for plasma HDL and subcutaneous fat pad mass.

References

• Original: J:69682 Drake TA, et al., Genetic loci determining bone density in mice with diet-induced atherosclerosis. Physiol Genomics. 2001 Apr 27;5(4):205-15
• All: 2 reference(s)