Use Of Animal Models To Study Genes That Modulate Atherosclerosis

在过去的一年里，我们已经制造了几种新的转基因小鼠品系。 我们最近使用Tet-ON或Tet-off启动子制备了可逆的ApoE-KO小鼠。 通过在水中加入强力霉素，我们可以可逆地控制ApoE的表达，从而控制血脂异常的存在。 这些小鼠将用于正在进行的研究，检查各种饮食操作或治疗对动脉粥样硬化消退的影响。 这应该与常用的动脉粥样硬化进展小鼠模型更具临床相关性。 我们还生产了LCAT-KO x SREBP-tg小鼠，它们产生LpX，LpX是一种致病性脂蛋白颗粒，可导致LCAT基因缺陷患者的肾衰竭。 我们计划使用这些小鼠来测试重组LCAT作为这种疾病的可能疗法。

In the past year, we have made several new transgenic mice lines. We recently made a reversible ApoE-KO mice using either the Tet-ON or Tet-off promoter. By adding doxycycline to their water we can reversible control the expression of ApoE and thus the presence of dyslipidemia. These mice will be useful for ongoing studies examining the effect of various dietary manipulations or therapeutics on atherosclerosis regression. This should be more clinically relevant the commonly used atherosclerosis progression mouse models. We also produced LCAT-KO x SREBP-tg mice, which produce LpX, the pathogenic lipoprotein particle that causes renal failure in patients with a genetic defect in LCAT. We plan to use these mice to test recombinant LCAT as a possible therapy for this disorder.