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

By Robert Feil, Daniel Metzger

Leading specialists offer well timed and accomplished info on equipment for conditional mutagenesis within the mouse (part 1) and their program to version human body structure and pathophysiology (part 2). It illustrates how subtle genetic manipulations of the mouse genome are hired to version human illnesses and to spot underlying molecular mechanisms. eventually the ebook considers the advance of recent medicines to regard them.

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3 Applications . . . . . . . . . . For a Regional Mutagenesis Screen . . . . Exploring the Function and Regulation of Genes and the Genomic Organisation . . . . . Creating Mouse Models for Human Pathologies . . . . . . . . . . . . . . . . . 40 41 4 Conclusion . . . . . . . . . . . . . . . . . . . 43 References . . . . . . . . . . . . . . . . . . . . 44 Abstract Together with numerous other genome modifications, chromosome engineering offers a very powerful tool to accelerate the functional analysis of the mammalian genome.

However, there is a limitation to this technique due to the necessity of analyzing 100–1,000 meioses to localise one mutation with a good resolution (Justice 1999). Thus, the mapping and identification of many mutations is an enormous task. By introducing a deletion, pseudo-recessive screens can be carried out, helping to unravel mutations with phenotypic consequences located inside the deleted interval (Fig. 4A). In addition, coat colour markers associated with the engineered deletion using MICER vectors make it possible to avoid a meticulous genotyping program (Adams et al.

2000; Goodwin et al. 2001). However, the chromosome derivatives required further extensive characterisation. Even though deletion of genomic fragments up to 30 kb could be achieved by homologous recombination in ES cells (Gu et al. 1993; Zhang et al. 1994), inducing welldefined larger rearrangements requires the use of the Cre/loxP technology either in vitro in ES cells (Ramirez-Solis et al. 1995; Smith et al. 1995; van Deursen et al. 1995) or in vivo (Herault et al. 1998; Puech et al. 2000; Spitz et al.

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