title: Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.
abstract: Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.
authors.affiliation: Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Ichise
authors.forename: Akiko
authors.initials: A
authors.lastname: Hori
authors.forename: Seiji
authors.initials: S
authors.lastname: Shiozawa
authors.forename: Saki
authors.initials: S
authors.lastname: Kondo
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kanegae
authors.forename: Izumu
authors.initials: I
authors.lastname: Saito
authors.forename: Taeko
authors.initials: T
authors.lastname: Ichise
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D050939:Gene Fusion; D005821:Genetic Techniques; D019426:Integrases / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D010641:Phenotype; D011995:Recombination, Genetic; D013629:Tamoxifen; D015533:Transcriptional Activation; D019076:Transgenes
chemical_list: D000952:Antigens, Polyomavirus Transforming; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases