Constitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia
Fadya H Mroue-Ruiz1, Bhoomi Desai1, Madison Garvin1
1Neuroscience Institute, Georgia State University.
Abstract:
CX3CR1-Cre mouse lines have produced important advancements in our understanding of microglial biology. Recent studies have demonstrated the adverse effects of tamoxifen-induced CX3CR1-Cre expression during development, which include changes in microglial density, phenotype, and DNA damage, as well as anxiety-like behavior. However, the unintended effects of constitutive CX3CR1-BAC-Cre expression remain unexplored. Here, we characterized the effects of CX3CR1-BAC-Cre expression on microglia in CX3CR1-BAC-Cre+/- and CX3CR1-BAC-Cre-/- male and female littermates during early postnatal development and adulthood in multiple brain regions. Additionally, we performed anxiety-like behavior tests to assess changes caused by Cre expression. We found that CX3CR1-BAC-Cre expression causes subtle region- and sex-specific changes in microglial density, volume, and morphology during development, but these changes normalized by adulthood in all brain regions except the hippocampus. No behavioral effects were found. Our findings suggest that the constitutive-Cre model might be less detrimental than the inducible model, and highlight the need for proper controls.
Insights
Constitutive CX3CR1-BAC-Cre expression causes minor, temporary changes in microglia during development. These effects resolve by adulthood, suggesting this model is less detrimental than inducible Cre systems.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- CX3CR1-Cre mouse models are crucial for studying microglia.
- Tamoxifen-induced CX3CR1-Cre causes developmental issues and behavioral changes.
- Effects of constitutive CX3CR1-BAC-Cre are unknown.
Purpose of the Study:
- Characterize effects of CX3CR1-BAC-Cre on microglia.
- Assess developmental and adult microglial changes.
- Evaluate behavioral impact of CX3CR1-BAC-Cre.
Main Methods:
- Utilized CX3CR1-BAC-Cre+/- and -/- littermates (male/female).
- Analyzed microglia in multiple brain regions during development and adulthood.
- Conducted anxiety-like behavior tests.
Main Results:
- CX3CR1-BAC-Cre caused subtle, region- and sex-specific microglial changes during development.
- Microglial changes normalized by adulthood, except in the hippocampus.
- No significant behavioral alterations were observed.
Conclusions:
- Constitutive CX3CR1-BAC-Cre appears less detrimental than inducible models.
- Careful consideration of controls is necessary when using Cre models.
- This study provides insights into microglial development and Cre-mediated effects.
