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Genetic Manipulation of the Mouse Developing Hypothalamus through In utero Electroporation
Published on: July 24, 2013
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.
Abstract:
To develop spatio-temporally controlled somatic mutagenesis in the adult mouse nervous system, we established transgenic mice expressing the tamoxifen-inducible Cre-ERT recombinase under the control of the mouse prion protein (PrP) promoter. Cre-ERT was expressed in most regions of the brain and in the retina of one transgenic line, whereas its expression was mostly restricted to the hippocampus and the cerebellum in another line. As tamoxifen efficiently induced Cre-mediated recombination in the various neuronal cell types expressing Cre-ERT in the brain of adult mice, the PrP-Cre-ERT lines should be valuable tools to study the functions of genes involved in neurodegenerative diseases or regeneration, and in complex processes such as behaviour, learning and memory. Some limitations of presently available reporter lines for Cre-mediated recombination in adult mouse CNS are discussed.
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.

