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Generation of Genetically Modified Mice through the Microinjection of Oocytes
Published on: June 15, 2017
Generation of an OMgp allelic series in mice
Jae K Lee1, Lauren C Case, Andrea F Chan
1Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, California 92093-0691, USA.
Abstract:
The very limited ability to regenerate axons after injury in the mature mammalian central nervous system (CNS) has been partly attributed to the growth restrictive nature of CNS myelin. Oligodendrocyte myelin glycoprotein (OMgp) was identified as a major myelin-derived inhibitor of axon growth. However, its role in axon regeneration in vivo is poorly understood. Here we describe the generation and molecular characterization of an OMgp allelic series. With a single gene targeting event and Cre/FLP mediated recombination, we generated an OMgp null allele with a LacZ reporter, one without a reporter gene, and an OMgp conditional allele. This allelic series will aid in the study of OMgp in adult CNS axon regeneration using mouse models of spinal cord injury. The conditional allele will overcome developmental compensation when employed with an inducible Cre, and allows for the study of temporal and tissue/cell type-specific roles of OMgp in CNS injury-induced axonal plasticity.
Insights
Researchers developed new tools to study how myelin inhibits axon regeneration after central nervous system (CNS) injury. This work will help understand oligodendrocyte myelin glycoprotein (OMgp) roles in spinal cord injury repair.
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Mammalian central nervous system (CNS) axon regeneration is limited after injury.
- CNS myelin contains inhibitors, such as oligodendrocyte myelin glycoprotein (OMgp), that restrict axon growth.
- The in vivo role of OMgp in axon regeneration remains unclear.
Purpose of the Study:
- To generate and characterize a series of OMgp alleles for studying its function in CNS axon regeneration.
- To create tools for investigating OMgp's role in mouse models of spinal cord injury.
Main Methods:
- Utilized a single gene targeting event with Cre/FLP-mediated recombination.
- Generated OMgp null alleles (with and without LacZ reporter) and a conditional OMgp allele.
- Developed tools for studying OMgp in adult CNS axon regeneration and spinal cord injury models.
Main Results:
- Successfully generated a molecularly characterized OMgp allelic series.
- Created tools enabling the study of OMgp in adult CNS axon regeneration.
- The conditional allele allows for overcoming developmental compensation and studying temporal/tissue-specific roles.
Conclusions:
- The generated OMgp allelic series provides valuable tools for investigating OMgp's role in CNS axon regeneration.
- These tools will facilitate research into spinal cord injury repair and axonal plasticity.
- The conditional allele offers a novel approach to dissect OMgp function in vivo.
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