title: Rapid induction of large chromosomal deletions by a Cre/inverted loxP system in mouse ES Cell hybrids.
abstract: Loss of heterozygosity by whole or partial loss of chromosomal regions is crucial to genetic disorders, cancers and diseases. It is difficult to analyze the mechanisms of pathogenesis caused by large-scale chromosomal abnormalities due to the extreme rarity of this mutagenesis. Using a Cre/inverted loxP system, we have generated a chromosome elimination cassette (CEC) that induces a selective loss of embryonic-stem-cell-derived chromosomes in undifferentiated embryonic stem cell-somatic cell hybrids. Here, due to the increased expression of Cre, rapid formation of Cre recombination products and immediate loss of CEC-tagged chromosomes were detected by fluorescence in situ hybridization. Cre also initiated intrachromosomal recombination between identical short sequences outside loxP, leading to large chromosomal deletions of CEC-tagged regions. The Cre-mediated antiparallel synapses likely act as a scaffold to bring the identical short sequences into close proximity for recombination. This CEC technology might allow better understanding of the modulator sequences responsible for the tangled structure formation and its solution mechanism, inducing mitotic recombination leading to chromosomal deletions.
authors: ReproCELL, Inc., 3-16-13 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan.
authors: Tomomi
authors: T
authors: Otsuji
authors: Hiroyuki
authors: H
authors: Matsumura
authors: Tatsuya
authors: T
authors: Suzuki
authors: Norio
authors: N
authors: Nakatsuji
authors: Takashi
authors: T
authors: Tada
authors: Masako
authors: M
authors: Tada
mesh_terms: D000818:Animals; D002460:Cell Line; D002678:Chimera / Q000235:genetics; D002872:Chromosome Deletion; D053595:Embryonic Stem Cells; D005821:Genetic Techniques; D017404:In Situ Hybridization, Fluorescence; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D019656:Loss of Heterozygosity / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011995:Recombination, Genetic
chemical_list: C045073:Cre recombinase; D019426:Integrases