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  4. An ATF3-CreERT2 Knock-In Mouse for Axotomy-Induced Genetic Editing: Proof of Principle

An ATF3-CreERT2 Knock-In Mouse for Axotomy-Induced Genetic Editing: Proof of Principle

eNeuro, 2019 · DOI: https://doi.org/10.1523/ENEURO.0025-19.2019 · Published: March 28, 2019

Regenerative MedicineNeurologyGenetics

Simple Explanation

Researchers created a new mouse model to selectively edit the genes of injured neurons. They used a Cre-ERT2 construct driven by ATF3, a marker of nerve damage, to activate gene editing only in injured neurons. When crossed with reporter mice, recombination occurred only in injured neurons following sciatic nerve injury or spinal hemisection, indicating that the system works as intended. This new tool allows scientists to study the genetic control of injury responses and regeneration in a more targeted way, by editing genes only in the neurons that are affected by the injury.

Study Duration
28 days
Participants
Mice between two and four months of age
Evidence Level
Not specified

Key Findings

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    The ATF3-CreERT2 mouse line allows for selective genetic editing of injured neurons after peripheral nerve injury (PNI) and spinal cord injury.
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    Loss of ATF3 function delays functional recovery following sciatic nerve crush, indicating a previously unreported haploinsufficiency.
  • 3
    Injury-induced PTEN excision using the ATF3-CreERT2 line improves axonal regeneration and functional recovery after PNI.

Research Summary

The study presents a novel transgenic mouse model, ATF3-CreERT2, for selective genetic editing of injured neurons. The ATF3-CreERT2 line facilitates recombination specifically in axotomized neurons, enabling researchers to study the genetic control of injury responses and regeneration. The model's utility is demonstrated through PTEN excision, leading to improved axonal regeneration and functional recovery after peripheral nerve injury.

Practical Implications

Targeted Gene Editing

The ATF3-CreERT2 mouse line enables precise genetic manipulation of injured neurons, allowing researchers to investigate specific genes involved in injury responses and regeneration.

Understanding Neurotrauma

By selectively editing the genome of injured neurons, this model can help elucidate the molecular mechanisms underlying neurotrauma and identify potential therapeutic targets.

Regenerative Medicine

The ability to enhance axonal regeneration through targeted gene excision, such as PTEN, offers new avenues for developing strategies to promote nerve repair and functional recovery after injury.

Study Limitations

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