Cre-Lox Recombination - History

History

Cre-Lox recombination is a special type of site-specific recombination developed by Dr. Brian Sauer initially for use in activating gene expression in mammalian cell lines and transgenic mice (DuPont). Subsequently, the laboratory of Dr. Jamey Marth showed that Cre-Lox recombination could be used to delete loxP-flanked chromosomal DNA sequences at high efficiency in selected cell types of transgenic animals, suggesting this approach as a means to define gene function in specific cell types, indelibly mark progenitors in cell fate determination studies, induce specific chromosomal rearrangements for biological and disease modeling, and determine the roles of early genetic lesions in disease (and phenotype) maintenance. Shortly thereafter, the laboratory of Dr. Klaus Rajewsky reported the production of pluripotent embryonic stem cells bearing a targeted loxP-flanked (floxed) DNA polymerase gene. Combining these advances in collaboration, the laboratories of Drs. Marth and Rajewsky showed in 1994 that Cre-lox recombination could be used for conditional gene targeting in vivo. This technique continues to be used by hundreds of researchers and laboratories around the world as an essential procedure to discover gene function in normal and disease biology, resulting in numerous important discoveries that would otherwise have not been possible. In 2009, Germany awarded the Max Delbrück medal to Dr. Klaus Rajewsky for his role in developing Cre-Lox recombination. Cre-Lox recombination involves the targeting of a specific sequence of DNA and splicing it with the help of an enzyme called Cre recombinase. Because systemic inactivation of many genes further cause embryonic lethality, Cre-Lox recombination is commonly used to circumvent this problem. In addition, Cre–Lox recombination provides the best experimental control that presently exists in transgenic animal modeling to link genotypes (alterations in genomic DNA) to the biological outcomes (phenotypes).