The Jackson Laboratory, Bar Harbor, Maine, USA.
Physiol Genomics. 2010 Nov 29;42A(4):228-34. doi: 10.1152/physiolgenomics.00044.2010. Epub 2010 Sep 21.
Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J × DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain.
应激环境因素，如高脂肪饮食，可以诱导基因表达的变化，以维持生理内稳态。我们观察到不同近交系小鼠对高脂肪饮食的反应中，血浆高密度脂蛋白（HDL）胆固醇浓度存在差异。包括 C57BL/6J 在内的几种品系，其血浆 HDL 水平不受饮食影响而保持稳定，而包括 DBA2/J 在内的其他品系，其血浆 HDL 则发生明显变化。为了进一步探讨这一现象，我们利用 C57BL/6J×DBA/2J 杂交的公共数据，鉴定出与高脂肪饮食条件下 HDL 相关的遗传因素。我们的分析确定了一种上位性相互作用，在 C57BL/6J 小鼠的 HDL 水平缓冲中发挥作用，我们已经鉴定出 Arl4d 作为介导这种作用的候选基因。结构建模进一步阐明了遗传因素的相互作用，这些因素有助于 C57BL/6J 品系对高脂肪饮食的 HDL 反应的稳健性。
