From mouse to man: generating megabase chromosome rearrangements

Experimental approaches for deciphering the function of human genes rely he avily on our ability to generate mutations in model organisms such as the m ouse. However, because recessive mutations are masked by the wild-type alle le in the diploid context, conventional mutagenesis and screening is often laborious and costly. Chromosome engineering combines the power of gene tar geting in embryonic stem (ES) cells with Cre-loxP technology to create mice that are functionally haploid in discrete portions of the genome. Chromoso me deletions, duplications and inversions can be tagged with visible marker s, facilitating strain maintenance. These approaches allow for more refined mutagenesis screens that will greatly accelerate functional mouse genomics and generate mammalian models for developmental processes and cancer.