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We developed mouse lines that express either Cre recombinase (Cre) for constitutive targeting, or destabilized\u2010domain Cre recombinase (DD\u2010Cre) for inducible targeting from the\n                    <jats:italic>Cst7<\/jats:italic>\n                    locus (\n                    <jats:italic>Cst7<\/jats:italic>\n                    <jats:sup>DD\u2010Cre<\/jats:sup>\n                    ) to specifically manipulate disease associated microglia (DAM) and crossed with Ai14 tdTomato cre\u2010reporter line mice. Cst7\n                    <jats:sup>Cre<\/jats:sup>\n                    was found to target all brain resident myeloid cells, due to transient developmental expression of Cst7, but no expression was found in the inducible\n                    <jats:italic>Cst7<\/jats:italic>\n                    <jats:sup>DD\u2010Cre<\/jats:sup>\n                    mice. Further crossing of this line with 5xFAD mice combined with dietary administration of trimethoprim to induce DD\u2010Cre activity produces long\u2010term labeling in DAM without evidence of leakiness, with tdTomato\u2010expression restricted to cells surrounding plaques. Using this model, we found that DAMs are a subset of plaque\u2010associated 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\u2010labeled PAMs. These models allow either complete cre\u2010loxP targeting of all brain myeloid cells (Cst7\n                    <jats:sup>Cre<\/jats:sup>\n                    ), or inducible targeting of DAMs, without leakiness (\n                    <jats:italic>Cst7<\/jats:italic>\n                    <jats:sup>DD\u2010Cre<\/jats:sup>\n                    ).\n                  <\/jats:p>","DOI":"10.1002\/glia.70004","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T18:53:06Z","timestamp":1741719186000},"page":"1272-1287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Generation of an Inducible Destabilized\u2010Domain Cre Mouse Line to Target Disease Associated 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