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In the field of genetics, Cre-Lox recombination is known as a site-specific recombinase technology, and is widely used to carry out deletions, insertions, translocations and inversions at specific sites in the DNA of cells. It allows the DNA modification to be targeted to a specific cell type or be triggered by a specific external stimulus. It is implemented both in eukaryotic and prokaryotic systems. The system consists of a single enzyme, Cre recombinase, that recombines a pair of short target sequences called the ''Lox'' sequences. This system can be implemented without inserting any extra supporting proteins or sequences. The Cre enzyme and the original ''Lox'' site called the ''LoxP'' sequence are derived from bacteriophage P1. Placing Lox sequences appropriately allows genes to be activated, repressed, or exchanged for other genes. At a DNA level many types of manipulations can be carried out. The activity of the Cre enzyme can be controlled so that it is expressed in a particular cell type or triggered by an external stimulus like a chemical signal or a heat shock. These targeted DNA changes are useful in cell lineage tracing and when mutants are lethal if expressed globally. The Cre-Lox system is very similar in action and in usage to the FLP-FRT recombination system. ==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 (DuPont). Subsequently, researchers in the laboratory of Dr. Jamey Marth demonstrated that Cre-Lox recombination could be used to delete loxP-flanked chromosomal DNA sequences at high efficiency in selected cell types of transgenic animals, with the authors proposing that this approach could be used to define endogenous 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.〔Orban, P.C., Chui, D., and Marth, J.D. (1992) "Tissue– and site–specific recombination in transgenic mice." "Proc. Natl. Acad. Sci. USA" "89": 6861–6865〕 Shortly thereafter, researchers in the laboratory of Dr. Klaus Rajewsky reported the production of pluripotent embryonic stem cells bearing a targeted loxP-flanked (floxed) DNA polymerase gene.〔Gu, H., Zou, Y.R., and Rajewsky, K. (1993) "Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre–loxP–mediated gene targeting." "Cell" "73": 1155-1564〕 Combining these advances in collaboration, the laboratories of Drs. Marth and Rajewsky reported in 1994 that Cre-lox recombination could be used for conditional gene targeting in vivo.〔Gu, H., Marth, J.D., Orban, P.C., Mossman, H., and Rajewsky, K. (1994) "Deletion of the DNA polymerase beta gene in T cells using tissue-specific gene targeting. "Science" "265": 103-106.〕 However, they observed only ~50% of the DNA polymerase beta gene was deleted based on DNA blotting. It was unclear whether only one allele in each T-cell or 50% of T cells had 100% deletion in both alleles. The researchers were not sure whether this partial Cre-Lox recombination was due to the allelic site of recombination as it was clear from previous studies that Cre recombination did not require cells undergoing mitosis. Researchers have since reported complete Cre-Lox conditional gene mutagenesis in post-mitotic T cells by the Marth laboratory in 1995 〔Hennet et al.1995, T-cell specific deletion of a polypeptide N-acetylgalactosaminyltransferase gene by site-directed recombination. Proc. Natl. Acad. Sci. USA. 92:12070-74〕 and independently by Joe Z. Tsien and his colleagues in the post-mitotic neurons in the adult brain.〔Tsien et al. 1996, Subregion- and cell type-restricted gene knockout in mouse brain.Cell. 87(7):1317-26.〕 These developments have led to a wide-spread use of conditional mutagenesis in biomedical research, spanning many disciplines in which it becomes a powerful platform for determining gene function in specific cell types and at specific developmental times. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Cre-Lox recombination」の詳細全文を読む スポンサード リンク
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