Chromosome engineering in mice

摘要: Chromosomal rearrangements are the major cause of inherited human disease and fetal loss. Translocations loss heterozygosity important genetic changes causally involved in neoplasia. variants, such as deficiencies, commonly exploited screens organisms Drosophila because a small portion genome is functionally hemizygous. In mouse, deficiencies not generally available, thus for recessive mutations cumbersome. We report here that defined inversions duplications extending to 3-4 cM can be constructed embryonic stem cells. This was achieved by consecutive targeting loxP recombination substrates end points interval followed Cre-induced recombination. reconstructs positive selectable marker which facilitates direct selection clones with chromosome structure specific relative orientation sites. Duplication deletion alleles have been transmitted into mouse germ line. The availability mice regions segmental haploidy will allow their use enable accurate models 'chromosomal' diseases generated.