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Article Abstract
Unlabelled: The function of microglia during progression of Alzheimer's disease (AD) can be investigated using mouse models that enable genetic manipulation of microglial subpopulations in a temporal manner. We developed a mouse strain that expresses destabilized-domain Cre recombinase (DD-Cre) from the locus ( ) and tested this in 5xFAD amyloidogenic, Ai14 tdTomato cre-reporter line mice. Dietary administration of trimethoprim to induce DD-Cre activity produces long-term labeling in disease associated microglia (DAM) without evidence of leakiness, with tdTomato-expression restricted to cells surrounding plaques. Using this model, we found that DAMs are a subset of plaque-associated microglia (PAMs) and their transition to DAM increases with age and disease stage. Spatial transcriptomic analysis revealed that tdTomato+ cells show higher expression of disease and inflammatory genes compared to other microglial populations, including non-labeled PAMs. This model should allow inducible cre-loxP targeting of DAMs, without leakiness.
Highlights: We developed a new mouse strain which specifically enables recombination of loxP sites in disease associated microglia (DAMs) and can be used to manipulate DAM-gene expression.DAMs represent a subset of plaque associated microglia (PAMs), and DAM expression increases with disease progression.Spatial transcriptomic analyses reveal that DAMs have higher expression of disease and inflammatory genes compared to other PAMs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429805 | PMC |
| http://dx.doi.org/10.1101/2024.09.18.613773 | DOI Listing |
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