Temporally controlled targeted somatic mutagenesis in the mouse brain

P Weber1, D Metzger, P Chambon

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de la Recherche Scientifique, Collège de France, Université Louis Pasteur, BP163, 67404 Illkirch-Cedex, Communauté Urbaine de Strasbourg, France.

Insights

Researchers developed new transgenic mice for precise genetic study in the adult mouse nervous system. These prion protein promoter (PrP-Cre-ERT) mice enable tamoxifen-controlled gene manipulation for studying brain function and disease.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Studying gene function in the adult nervous system requires precise temporal and spatial control.
  • Existing methods for somatic mutagenesis in the central nervous system (CNS) have limitations.

Purpose of the Study:

  • To develop a novel tool for spatio-temporally controlled somatic mutagenesis in the adult mouse nervous system.
  • To establish and characterize transgenic mouse lines expressing a tamoxifen-inducible Cre-ERT recombinase under the prion protein (PrP) promoter.

Main Methods:

  • Generation of transgenic mice expressing Cre-ERT under the PrP promoter.
  • Analysis of Cre-ERT expression patterns in different brain regions and the retina.
  • Induction of Cre-mediated recombination using tamoxifen in adult mice.

Main Results:

  • Two transgenic mouse lines were established with distinct Cre-ERT expression patterns.
  • Cre-ERT expression was observed in widespread brain regions and retina in one line, and restricted to hippocampus and cerebellum in another.
  • Tamoxifen efficiently induced Cre-mediated recombination in various neuronal cell types.

Conclusions:

  • The PrP-Cre-ERT mouse lines provide a valuable tool for inducible gene manipulation in the adult mouse brain.
  • These lines are suitable for studying gene function in neurodegenerative diseases, regeneration, behavior, learning, and memory.
  • Further development of reporter lines for CNS recombination is needed.