Targeted expression of Cre recombinase provokes placental-specific DNA recombination in transgenic mice

PLoS One. 2012;7(2):e29236. doi: 10.1371/journal.pone.0029236. Epub 2012 Feb 17.

Abstract

Background: Inadequate placental development is associated with a high incidence of early embryonic lethality and serious pregnancy disorders in both humans and mice. However, the lack of well-defined trophoblast-specific gene regulatory elements has hampered investigations regarding the role of specific genes in placental development and fetal growth.

Principal findings: By random assembly of placental enhancers from two previously characterized genes, trophoblast specific protein α (Tpbpa) and adenosine deaminase (Ada), we identified a chimeric Tpbpa/Ada enhancer that when combined with the basal Ada promoter provided the highest luciferase activity in cultured human trophoblast cells, in comparison with non-trophoblast cell lines. We used this chimeric enhancer arrangement to drive the expression of a Cre recombinase transgene in the placentas of transgenic mice. Cre transgene expression occurred throughout the placenta but not in maternal organs examined or in the fetus.

Significance: In conclusion, we have provided both in vitro and in vivo evidence for a novel genetic system to achieve placental transgene expression by the use of a chimeric Tpbpa/Ada enhancer driven transgene. The availability of this expression vector provides transgenic opportunities to direct the production of desired proteins to the placenta.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / genetics
  • Animals
  • Cell Line
  • Cells, Cultured
  • DNA / genetics*
  • Enhancer Elements, Genetic / genetics
  • Female
  • Gene Expression Regulation
  • Gene Targeting*
  • Genes, Reporter / genetics
  • Humans
  • Integrases / metabolism*
  • Luciferases / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Organ Specificity / genetics
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Proteins / genetics
  • Promoter Regions, Genetic / genetics
  • Recombination, Genetic / genetics*
  • Transcription, Genetic
  • Transgenes / genetics
  • Trophoblasts / metabolism

Substances

  • Pregnancy Proteins
  • Tpbpa protein, mouse
  • DNA
  • Luciferases
  • Cre recombinase
  • Integrases
  • Adenosine Deaminase