title: Drug-inducible gene recombination by the Dppa3-MER Cre MER transgene in the developmental cycle of the germ cell lineage in mice.
abstract: Germ cells ensure the diversification and totipotency of genetic information via the elaborate genetic and epigenetic regulation of the genome architecture during their development. To understand the mechanism underlying the regulation of genome function in germ cells, it is of primary importance to develop systems in which gene function can be regulated at desired time points during their development. Here, we report the generation of transgenic strains that express Cre recombinase flanked by the ligand-binding domains of murine estrogen receptor (MER Cre MER [MCM]) under the control of the regulatory elements of the Dppa3 (also known as Stella or Pgc7) gene. On the administration of 4-hydroxytamoxifen (4-OHT), the Dppa3-MCM strains recombined the sequence flanked by the loxP elements (the floxed sequence) specifically in primordial germ cells as early as Embryonic Day (E) 7.0, and this recombination became robust after E9.5. Furthermore, these strains exhibited efficient and specific recombination of the floxed sequence during the growth of oocytes and in preimplantation embryos in the 4-OHT-dependent manner. Thus, these Dppa3-MCM strains offer valuable opportunities to explore gene function in both loss-of-function and gain-of-function experiments at a variety of time points during germ cell development.
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hirota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.forename: Mayo
authors.initials: M
authors.lastname: Shigeta
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niwa
authors.forename: Mitinori
authors.initials: M
authors.lastname: Saitou
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017930:Genes, Reporter; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D000076202:c-Mer Tyrosine Kinase
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C462180:Dppa3 protein, mouse; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D013629:Tamoxifen; C016601:afimoxifene; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; C045073:Cre recombinase; D019426:Integrases