Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase

Curr Biol. 1998 Dec 3;8(24):1323-6. doi: 10.1016/s0960-9822(07)00562-3.

Abstract

The ability to generate specific genetic modifications in mice provides a powerful approach to assess gene function. When genetic modifications have been generated in the germ line, however, the resulting phenotype often only reflects the first time a gene has an influence on - or is necessary for - a particular biological process. Therefore, systems allowing conditional genetic modification have been developed (for a review, see [1]); for example, inducible forms of the Cre recombinase from P1 phage have been generated that can catalyse intramolecular recombination between target recognition sequences (loxP sites) in response to ligand [2] [3] [4] [5]. Here, we assessed whether a tamoxifen-inducible form of Cre recombinase (Cre-ERTM) could be used to modify gene activity in the mouse embryo in utero. Using the enhancer of the Wnt1 gene to restrict the expression of Cre-ERTM to the embryonic neural tube, we found that a single injection of tamoxifen into pregnant mice induced Cre-mediated recombination within the embryonic central nervous system, thereby activating expression of a reporter gene. Induction was ligand dependent, rapid and efficient. The results demonstrate that tamoxifen-inducible recombination can be used to effectively modify gene function in the mouse embryo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / embryology
  • Central Nervous System / enzymology
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / enzymology*
  • Enhancer Elements, Genetic
  • Enzyme Induction / drug effects
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Genes, Reporter / drug effects
  • Integrases / biosynthesis*
  • Integrases / genetics*
  • Mice
  • Mice, Transgenic
  • Pregnancy
  • Proto-Oncogene Proteins / genetics
  • Recombination, Genetic / drug effects*
  • Tamoxifen / pharmacology*
  • Viral Proteins*
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins*
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics

Substances

  • Proto-Oncogene Proteins
  • Viral Proteins
  • Wnt Proteins
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Zebrafish Proteins
  • Tamoxifen
  • Cre recombinase
  • Integrases
  • beta-Galactosidase