Use Of Animal Models To Study Genes That Modulate Atherosclerosis

使用动物模型研究调节动脉粥样硬化的基因

• 批准号: 8939766
• 负责人: Alan Thomas Remaley
• 金额: $ 126.26万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8939766
• 关键词: Affect; Animal Model; Apolipoprotein E; Atherosclerosis; Coronary heart disease; Diet; Disease; Doxycycline; Dyslipidemias; Genes; Kidney Failure; Lipoproteins; Metabolism; Mus; Mutation; Patients; Phosphatidylcholine-Sterol O-Acyltransferase; Recombinants; Testing; Tetanus Helper Peptide; Therapeutic; Transgenic Mice; Water; clinically relevant; in vivo; lipid metabolism; mouse model; particle; promoter

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.

在过去的一年中，我们制作了几条新的转基因小鼠线。 最近，我们使用Tet-On或Tet-Owt启动子制作了可逆的APOE-KO小鼠。 通过在水中添加多西环素，我们可以可逆地控制APOE的表达，从而存在血脂异常的存在。 这些小鼠将对研究各种饮食操纵或治疗剂对动脉粥样硬化消退的影响很有用。 这应该在临床上更相关。通常使用的动脉粥样硬化进展小鼠模型。 我们还产生了LCAT-KO X SREBP-TG小鼠，该小鼠产生LPX，这是导致LCAT遗传缺陷患者肾衰竭的致病性脂蛋白颗粒。 我们计划使用这些小鼠测试重组LCAT作为该疾病的可能疗法。