| First Author | Zhang X | Year | 2021 |
| Journal | Glia | Volume | 69 |
| Issue | 3 | Pages | 729-745 |
| PubMed ID | 33068332 | Mgi Jnum | J:303683 |
| Mgi Id | MGI:6509536 | Doi | 10.1002/glia.23925 |
| Citation | Zhang X, et al. (2021) Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement. Glia 69(3):729-745 |
| abstractText | The DNA excision repair protein Ercc1 is important for nucleotide excision, double strand DNA break, and interstrand DNA crosslink repair. In constitutive Ercc1-knockout mice, microglia display increased phagocytosis, proliferation and an enhanced responsiveness to lipopolysaccharide (LPS)-induced peripheral inflammation. However, the intrinsic effects of Ercc1-deficiency on microglia are unclear. In this study, Ercc1 was 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 after Ercc1 deletion. Larger and more ramified microglia were observed following Ercc1 deletion 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 functional Ercc1 allele. In contrast to constitutive Ercc1-deficient mice, microglia-specific deletion of Ercc1 did not induce microglia activation or increase their responsiveness to a systemic LPS challenge. Gene expression analysis suggested that Ercc1 deletion in microglia induced a transient aging signature, which was different from a priming or disease-associated microglia gene expression profile. |
