Lost in Transgenesis: A Users guide for Genetically Manipulating the Mouse in Cardiac Research

摘要

The advent of modern mouse genetics has benefited many fields of diseased-based research over the past 20 years, none perhaps more profoundly than cardiac biology. Indeed, the heart is now arguably one of the easiest tissues to genetically manipulate given the availability of an ever-growing tool chest of molecular reagents/promoters and “facilitator” mouse lines. It is now possible to modify the expression of essentially any gene or partial gene-product in the mouse heart at any time, either gain- or loss-of-function. This review is designed as a handbook for the non-mouse geneticist and/or junior investigator to permit the successful manipulation of any gene or RNA product in the heart, while avoiding artifacts. Here guidelines, pitfalls, and limitations are presented so that rigorous and appropriate examination of cardiac genotype-phenotype relationships can be performed. This review utilizes examples from the field to illustrate the vast spectrum of experimental and design details that need to be considered when using genetically modified mouse models to study cardiac biology.