Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Semin Cell Dev Biol. 2018 Sep;81:98-109. doi: 10.1016/j.semcdb.2017.07.011. Epub 2017 Jul 20.
Sterol regulatory element-binding proteins (SREBPs), master transcriptional regulators of cholesterol and fatty acid synthesis, have been found to contribute to a diverse array of cellular processes. In this review, we focus on genetically engineered mice in which the activities of six components of the SREBP gene pathway, namely SREBP-1, SREBP-2, Scap, Insig-1, Insig-2, or Site-1 protease have been altered through gene knockout or transgenic approaches. In addition to the expected impacts on lipid metabolism, manipulation of these genes in mice is found to affect a wide array of developmental and physiologic processes ranging from interferon signaling in macrophages to synaptic transmission in the brain. The findings reviewed herein provide a blueprint to guide future studies defining the complex interactions between lipid biology and the physiologic processes of many distinct organ systems.
固醇调节元件结合蛋白（SREBPs）是胆固醇和脂肪酸合成的主要转录调控因子，现已发现其参与了多种细胞过程。在这篇综述中，我们重点介绍了通过基因敲除或转基因方法改变 SREBP 基因途径的六个组成部分（即 SREBP-1、SREBP-2、Scap、Insig-1、Insig-2 或 Site-1 蛋白酶）的活性的基因工程小鼠。除了对脂质代谢的预期影响外，还发现这些基因在小鼠中的操纵会影响从巨噬细胞中的干扰素信号传导到大脑中的突触传递等广泛的发育和生理过程。本文综述的研究结果为指导未来的研究提供了蓝图，这些研究定义了脂质生物学与许多不同器官系统的生理过程之间的复杂相互作用。
