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diff --git a/general/datasets/Epfladel1013/summary.rtf b/general/datasets/Epfladel1013/summary.rtf new file mode 100644 index 0000000..07c710f --- /dev/null +++ b/general/datasets/Epfladel1013/summary.rtf @@ -0,0 +1 @@ +<p>The BXD genetic reference population is a recombinant inbred panel descended from crosses between the C57BL/6 (B6) and DBA/2 (D2) strains of mice, which segregate for about 5 million sequence variants. Recently, some these variants have been established with effects on general metabolic phenotypes such as glucose response and bone strength. We here phenotype 43 BXD strains and observe they have large variation (~5-fold) in their spontaneous activity during waking hours. QTL analyses indicate that ~40% of this variance is attributable to a narrow locus containing the aryl hydrocarbon receptor (<em>Ahr</em>)<em>,</em> a basic helix-loop-helix transcription factor with well-established roles in development and xenobiotic metabolism. Strains with the D2 allele of <em>Ahr</em> have reduced gene expression compared to those with the B6 allele, and have significantly higher spontaneous activity. This effect was also observed in B6 mice with a congenic D2 <em>Ahr</em> interval, and in B6 mice with a humanized <em>AHR</em> allele which, like the D2 allele, is expressed much less and has less enzymatic activity than the B6 allele. <em>Ahr </em>is highly conserved in invertebrates, and strikingly inhibition of its orthologs in <em>D. melanogaster</em> and <em>C. elegans </em>(<em>spineless</em> and <em>ahr-1</em>) leads to marked increases in basal activity. In mammals, <em>Ahr</em> has numerous ligands, but most are either non-selective (e.g. resveratrol) or highly toxic (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)). Thus, we chose to examine a major environmental influence—long term feeding with high fat diet (HFD)—to see if the effects of <em>Ahr</em> are dependent on major metabolic differences. Interestingly, while HFD robustly halved movement across all strains, the QTL position and effects of <em>Ahr</em> remained unchanged, indicating that the effects are independent. The highly consistent effects of <em>Ahr </em>on movement indicate that changes in its constitutive activity have a role on spontaneous movement and may influence human behavior. </p>
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