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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.
The European Journal of Neuroscience
|February 28, 2002
Summary
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.