Advertisement

Transgenic Research

, Volume 10, Issue 6, pp 545–553 | Cite as

Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice

  • Kay-Uwe Wagner
  • Toni Ward
  • Barbara Davis
  • Roger Wiseman
  • Lothar Hennighausen
Article

Abstract

Cre-loxP based gene deletion approaches hold great promise to enhance our understanding of molecular pathways controlling mammary development and breast cancer. We reported earlier the generation of transgenic mice that express the Cre recombinase under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). These mice have become a valuable research tool to delete genes specifically in the mammary gland, other secretory organs, and the female germline. We have now characterized in depth the expression of the MMTV-Cre transgene using the ROSA26-lox-Stop-lox-LacZ reporter strain to determine the temporal and spatial activation of Cre on the level of single cells. Our results show that MMTV-mediated Cre-activation is restricted to specific cell types of various secretory tissues and the hematopoietic system. Secondly, the timing of Cre expression varies between tissues and cell types. Some tissues express Cre during embryonic development, while other selected cell types highly activate Cre around puberty, suggesting a strong influence of steroid hormones on the transcriptional activation of the MMTV-LTR. Thirdly, Cre expression in the female germline is restricted to individual mouse lines and is therefore dependent on the site of integration of the transgene. Information provided by this study will guide the researcher to those cell types and developmental stages at which a phenotype can be expected upon deletion of relevant genes.

Cre mammary MMTV-LTR ROSA26 transgenic mice 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gérard M, Hernandez L, Wevrick R and Stewart CL (1999) Disruption of the mouse necdin gene results in early post-natal lethality. Nature Genet 23: 199–202.Google Scholar
  2. Hoess R, Abremski K and Sternberg N (1984) The nature of the interaction of the P1 recombinase Cre with the recombining site LoxP. Cold Spring Harb Sym 49: 761–768.Google Scholar
  3. Hoess R, Wierzbicki A and Abremski K (1987) Isolation and characterization of intermediates in site-specific recombination. Proc Natl Acad Sci USA 84: 6840–6844.Google Scholar
  4. Loots GG, Locksley RM, Blakespoor CM, Wang ZE, Miller W, Rubin EM and Frazer KA (2000) Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288: 136–140.Google Scholar
  5. Nagy A (2000) Cre Recombinase: The universal reagent for genome tailoring. Genesis 26: 99–109.Google Scholar
  6. Rucker EB, Dierisseau P, Wagner K-U, Garrett L, Wynshaw-Boris A, Flaws JA and Hennighausen L (2000) Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol 14: 1038–1052.Google Scholar
  7. Soriano P (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nature Genet 21: 70–71.Google Scholar
  8. Wagner K-U, Wall RJ, St-Onge L, Gruss P, Wynshaw-Boris A, Garrett L, Li ML, Furth PA and Hennighausen L (1997) Cremediated gene deletion in the mammary gland. Nucl Acids Res 25: 4323–4330.Google Scholar
  9. Wagner K-U, Claudio E, Rucker III EB, Riedlinger G, Broussard P, Schwarzberg L, Siebenlist U and Hennighausen L (2000) Conditional deletion of the bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly. Development 127: 4949–4958.Google Scholar
  10. Xu XL, Wagner K-U, Larson D, Weaver Z, Li CL, Ried T, Hennighausen L, Wynshaw-Boris A and Deng C-X (1999) Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nature Genet 22: 37–43.Google Scholar
  11. Zambrowicz BP, Imamoto A, Fiering S, Herzenberg LA, Kerr WG and Soriano P (1997) Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA 94: 3789–3794.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Kay-Uwe Wagner
    • 1
    • 2
  • Toni Ward
    • 3
  • Barbara Davis
    • 3
  • Roger Wiseman
    • 3
  • Lothar Hennighausen
    • 2
  1. 1.Eppley Institute for Research in Cancer and Allied DiseasesUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Laboratory of Genetics and Physiology, National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)National Institutes of HealthBethesdaUSA
  3. 3.Laboratory of Women's Health, Building 101, C438Research Triangle ParkUSA

Personalised recommendations