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Updated: Sep 28, 2026

Induction of Leptomeningeal Cells Modification Via Intracisternal Injection
Published on: May 7, 2020
Inducible site-specific recombination in myelinating cells
Nathalie H Doerflinger1, Wendy B Macklin, Brian Popko
1Institut de Génétique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS, Université Louis Pasteur, Illkirch, France.
Abstract:
To explore the function of genes expressed by myelinating cells we have developed a model system that allows for the inducible ablation of predetermined genes in oligodendrocytes and Schwann cells. The Cre/loxP recombination system provides the opportunity to generate tissue-specific somatic mutations in mice. We have used a fusion protein between the Cre recombinase and a mutated ligand-binding domain of the human estrogen receptor (CreER(T)) to obtain inducible, site-specific recombination. CreER(T) expression was placed under the transcriptional control of the regulatory sequences of the myelin proteolipid protein (PLP) gene, which is abundantly expressed in oligodendrocytes and to a lesser extent in Schwann cells. The CreER(T) fusion protein translocated to the nucleus and mediated the recombination of a LacZ reporter transgene in myelinating cells of PLP/CreER(T) mice injected with the synthetic steroid tamoxifen. In untreated animals CreER(T) remained cytoplasmic, and there was no evidence of recombination. The PLP/ CreER(T) animals should be very useful in elucidating and distinguishing a particular gene's function in the formation and maintenance of the myelin sheath and in analyzing mature oligodendrocyte function in pathological conditions.
Insights
This study introduces a novel inducible gene ablation model in myelinating cells. This system allows researchers to precisely study gene functions in oligodendrocyte and Schwann cell development and disease.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Understanding gene function in myelinating cells is crucial for neurological research.
- Existing models lack precise temporal and cell-specific gene manipulation capabilities.
Purpose of the Study:
- To develop an inducible system for targeted gene ablation in oligodendrocytes and Schwann cells.
- To enable the study of gene function in myelin sheath formation, maintenance, and in pathological conditions.
Main Methods:
- Utilized the Cre/loxP recombination system for tissue-specific somatic mutations in mice.
- Engineered a fusion protein (CreER(T)) for inducible, site-specific recombination.
- Placed CreER(T) expression under the control of the myelin proteolipid protein (PLP) gene promoter.
- Administered tamoxifen to induce nuclear translocation of CreER(T) and recombination.
Main Results:
- Successfully generated myelinating cellspecific gene ablation in PLP/CreER(T) mice upon tamoxifen administration.
- Demonstrated tamoxifen-inducible nuclear translocation of CreER(T) and recombination of a LacZ reporter transgene.
- Confirmed no recombination in untreated animals, indicating tight regulation of the system.
Conclusions:
- The PLP/CreER(T) mouse model provides a powerful tool for inducible gene ablation in myelinating cells.
- This system facilitates the elucidation of gene functions in myelin sheath development and homeostasis.
- The model is valuable for studying oligodendrocyte function in disease contexts.
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