title: Target chromosomes of inducible deletion by a Cre/inverted loxP system in mouse embryonic stem cells.
abstract: Chromosomal deletions are widely involved in serious genetic diseases and in the pathogenesis of cancers. These deletions often generate loss of heterozygosity (LOH) of one of the alleles of a tumor suppressor gene. Because of the technical difficulty inherent in genetic manipulation studies of a chromosome-wide deficiency, it has not been experimentally determined whether chromosome deletions could be a trigger for cancer development. Using the Cre/inverted loxP system, we have developed a chromosome elimination cassette (CEC) that Cre-dependently induces whole or partial deletions of the CEC-tagged chromosomes. Most deletions are usually fatal, but diploid cells carrying small deletions have been obtained from mouse embryonic stem cells carrying a CEC transgene (CEC-ESC). Here, we further isolated various CEC-ESC clones and analyzed CEC integration sites using the fluorescence in-situ hybridization method. In 17 CEC-ESC clones possessing normal chromosome sets, 13 types of chromosomes out of 20 pairs of mouse chromosomes were tagged by CEC. Each CEC-tagged chromosome could become a future target for the creation of a Cre-inducible LOH by a combination of in vitro and in vivo genetic mutation.
authors.affiliation: ReproCELL Inc., Minato-ku, Tokyo, Japan. matada@frontier.kyoto-u.ac.jp
authors.forename: Masako
authors.initials: M
authors.lastname: Tada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsumura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kurose
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.forename: Takashi
authors.initials: T
authors.lastname: Tada