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Conditional transgenesis using Dimerizable Cre (DiCre).

Nicolas Jullien1, Isabelle Goddard, Samia Selmi-Ruby

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Researchers developed Dimerizable Cre (DiCre) for temporal control of genome engineering. This system uses rapamycin to activate Cre recombinase activity, enabling precise control over genetic modifications in experimental animals with low background activity.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Cre recombinase is crucial for genome engineering in experimental animals.
  • Current methods lack efficient temporal control over Cre recombinase activity.
  • A novel system, Dimerizable Cre (DiCre), was developed to address this limitation.

Purpose of the Study:

  • To develop and validate a rapamycin-inducible Cre recombinase system (DiCre) for temporal control of genetic recombination.
  • To assess the in vivo performance and efficiency of DiCre in mice.

Main Methods:

  • DiCre was generated by splitting Cre into two inactive moieties fused to FKBP12 and FRB.
  • DiCre was knocked-in into the Rosa26 locus of mice.
  • Mice were mated with indicator lines (Z/EG or R26R) and treated with rapamycin postnatally or in utero to assess recombination.

Main Results:

  • DiCre showed low background activity in the absence of rapamycin.
  • Postnatal rapamycin administration induced efficient recombination in various tissues (liver, heart, kidney, muscle).
  • In utero rapamycin treatment resulted in very low levels of recombination.

Conclusions:

  • DiCre system provides efficient temporal control over Cre recombinase activity.
  • DiCre enables the establishment of conditional Cre-deleter mouse lines.
  • The system allows for combinatorial control of recombination in specific cell populations based on dual promoter expression.