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Physiol. Genomics (December 14, 2004). doi:10.1152/physiolgenomics.00183.2004
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Submitted on August 12, 2004
Accepted on December 10, 2004

Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways

Ioannis M Stylianou1*, Michael Clinton2, Peter D Keightley3, Clare Pritchard4, Zuzzana Tymowska-Lalanne4, Lutz Bunger5, and Simon Horvat6

1 Department of Gene Expression, Roslin Institute, Edinburgh, Scotland, United Kingdom; School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom
2 Department of Gene Expression, Roslin Institute, Edinburgh, Scotland, United Kingdom
3 School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom
4 Mammalian Genetics Unit, MRC, Harwell, England, United Kingdom
5 Animal Breeding & Development, Sustainable Livestock Systems, SAC, Penicuik, Scotland, United Kingdom
6 Biotechnical Faculty, Zootechnical Department, University of Ljubljana, Slovenia; Department of Gene Expression, Roslin Institute, Edinburgh, Scotland, United Kingdom

* To whom correspondence should be addressed. E-mail: jstylian{at}jax.org.

Obesity related diseases are poised to become the primary cause of death in developed nations. While a number of monogenic causes of obesity have recently been identified, these are responsible for only a small proportion of human cases of obesity. Quantitative trait locus (QTL) studies using animal models have revealed hundreds of potential loci that affect obesity, however few have been further analyzed beyond the original QTL scan. We previously mapped four QTL in an F2 between divergently selected Fat (F) and Lean (L) lines. A QTL of large effect on chromosome 15 (Fob3) was subsequently mapped to a higher resolution into two smaller effect QTL (Fob3a and Fob3b) using crosses between the F-line and a congenic line containing L-line alleles at the Fob3 QTL region. Here we report the gene expression characterization of Fob3b. Microarray expression analysis using the NIA-NIH 15K cDNA array set containing 14938 mouse ESTs was employed to identify candidate genes and pathways that are differentially expressed between the F-line and a congenic line containing only the Fob3b QTL (Fob3b-line). Our study suggests squalene epoxidase (Sqle), a cholesterol biosynthesis enzyme, as a strong positional candidate gene for Fob3b. Several other cholesterol biosynthesis pathway genes unlinked to Fob3b were found to be differentially expressed, suggesting that a perturbation of this pathway could be in part responsible for the phenotypic difference between the F-line and Fob3b-line mice.




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