Conditional Animal Models for the Study of Lipid Metabolism and Lipid Disorders

Abstract

The advent of technologies that allow conditional mutagenesis has revolutionized our ability to explore gene functions and to establish animal models of human diseases. Both aspects have proven to be of particular importance in the study of lipid-related disorders. Classical approaches to gene inactivation by conventional gene targeting strategies have been successfully applied to generate animal models like the LDL receptor- and the apolipoprotein E-knockout mice, which are still widely used to study diverse aspects of atherosclerosis, lipid transport, and neurodegenerative disease. In many cases, however, simply inactivating the gene of interest has resulted in early lethal or complex phenotypes which are difficult to interpret. In recent years, additional tools have therefore been developed that allow the spatiotemporally controlled manipulation of the genome, as described in detail in Part I of this volume. Our aim is to provide an exemplary survey of the application of different conditional mutagenesis techniques in lipid research in order to illustrate their potential to unravel physiological functions of a broad range of genes involved in lipid homeostasis.

Models to Study Atherosclerosis: A Mechanistic Insight

“…It also describes in brief how these models can be used for the assessment of various drugs. Although reviews on animal models of atherosclerosis have been published [18][19][20][21][22][23][24], there are almost none for the in vitro, cell and target based models, which this review will cover. Besides updating all the models, the present review approaches the models in a mechanistic way and thus blends classical animal models with recent biochemical and molecular findings.…”

Purification of Plasmid and BAC Transgenic DNA Constructs

“…Transgenic and knockout mouse models have been extensively used in lipoprotein and atherosclerosis research [1-3] , just as in many other fields of biomedical research. A great majority of these transgenic lines were generated using the so-called pronuclear microinjection method.…”