Abstract
The DNA excision repair protein Ercc1 is important for nucleotide excision, double strand DNA break, and interstrand DNA crosslink repair. In constitutiveErcc1-knockout mice, microglia display increased phagocytosis, proliferation and an enhanced responsiveness to lipopolysaccharide (LPS)-induced peripheral inflammation. However, the intrinsic effects ofErcc1-deficiency on microglia are unclear. In this study,Ercc1was specifically deleted from Cx3cr1-expressing cells and changes in microglia morphology and immune responses at different times after deletion were determined. Microglia numbers were reduced with approximately 50% at 2-12 months afterErcc1deletion. Larger and more ramified microglia were observed followingErcc1deletion both in vivo and in organotypic hippocampal slice cultures.Ercc1-deficient microglia were progressively lost, and during this period, microglia proliferation was transiently increased.Ercc1-deficient microglia were gradually replaced by nondeficient microglia carrying a functionalErcc1allele. In contrast to constitutiveErcc1-deficient mice, microglia-specific deletion ofErcc1did not induce microglia activation or increase their responsiveness to a systemic LPS challenge. Gene expression analysis suggested thatErcc1deletion in microglia induced a transient aging signature, which was different from a priming or disease-associated microglia gene expression profile.
Original language | English |
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Article number | 23925 |
Pages (from-to) | 1-17 |
Number of pages | 17 |
Journal | Glia |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar-2021 |
Keywords
- aging
- DNA damage repair
- Ercc1
- microglia
- morphometrics
- DNA-DAMAGE
- MOUSE MODEL
- CELL
- NEURODEGENERATION
- REVEALS
- REPOPULATION
- ABLATION
- AGE
- TURNOVER