Conditional Mutagenesis: An Approach to Disease Models by Robert Feil, Daniel Metzger

By Robert Feil, Daniel Metzger

Leading specialists supply well timed and accomplished info on tools for conditional mutagenesis within the mouse (part 1) and their software to version human body structure and pathophysiology (part 2). It illustrates how subtle genetic manipulations of the mouse genome are hired to version human ailments and to spot underlying molecular mechanisms. ultimately the ebook considers the improvement of latest medications to regard them.

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Indeed Cre recombinase can act in the mammalian genome without any cofactor, allowing one to generate large chromosomal rearrangements either in culture or in the mouse. e. in cis, or in a trans configuration), their orientation (direct or inverted) and the localisation in homologous or heterologous chromosomes (Fig. 1). Cre/loxP-Mediated Chromosome Engineering of the Mouse Genome 31 Fig. 1 A–D Different types of rearrangements produced by the Cre/loxP recombination system depending on the position and orientation of the loxP sites.

2002), R26Cre (Soriano 1999) and CMV-Cre (Dupe et al. 1997) in which the Cre recombinase is expressed more or less ubiquitously or at least early during development in most of the tissues. An alternative to the ubiquitous Cre transgenic lines is the ZP3-Cre line (Lewandoski et al. 1997; de Vries et al. 2000), showing a high level of Cre expression during oogenesis before the first meiotic division. However, the recombination efficiency is not always high and this can lead to the generation of mosaic animals (Leneuve et al.

Science 269:1427–1429 Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR (1999) Tissuespecific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96:329–339 Kyrkanides S, Miller JH, Bowers WJ, Federoff HJ (2003) Transcriptional and posttranslational regulation of Cre recombinase by RU486 as the basis for an enhanced inducible expression system. Mol Ther 8:790–795 Lakso M, Sauer B, Mosinger B Jr, Lee EJ, Manning RW, Yu SH, Mulder KL, Westphal H (1992) Targeted oncogene activation by site-specific recombination in transgenic mice.

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