A Genetically Engineered Mouse Model of Inflammatory Brain Injury
This genetically engineered mouse model harnesses CRISPR/Cas-9 technology to introduce a precise single nucleotide mutation in the ADAR1 gene, resulting in a lysine-to-asparagine substitution. The process involves injecting a custom-designed guide RNA alongside template DNA into mouse zygotes, followed by embryo transfer and rigorous progeny screening via DNA sequencing. The model exhibits elevated type I interferon levels and spontaneous brain inflammation, effectively mirroring key neuroinflammatory features characteristic of Aicardi-Goutières syndrome. These attributes provide researchers with a robust tool for studying complex neuroimmune interactions in vivo.
Description
The technology is differentiated by its precision and physiological relevance, addressing limitations seen in earlier models such as incomplete recapitulation of human pathology. Unlike previous knockouts or in vitro approaches that fell short in mimicking systemic neuroinflammation, this model faithfully reproduces both molecular and cellular aspects of the disease. Its ability to trigger chronic interferon responses in neuronal tissues and simulate white matter damage establishes a novel framework for exploring disease mechanisms and testing therapeutic interventions, offering significant promise for advancing research into rare neuroinflammatory conditions.Applications
- Drug screening platform- Preclinical efficacy testing
- Therapeutic target validation
- Diagnostic biomarker discovery
- Neuroinflammatory disease modeling
Advantages
- Accurately replicates critical neuroinflammatory features of Aicardi-Goutières syndrome in a live animal model.- Enables detailed investigation of AGS pathogenesis and molecular mechanisms through precise genetic modification.
- Provides a superior research tool compared to existing models, overcoming limitations seen in other mouse and iPSC models.
- Facilitates drug development and screening for potential therapeutic interventions in neuroinflammatory and neurodegenerative diseases.