{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:35:00Z","timestamp":1768516500112,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,19]]},"group-title":"Neuroscience","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,19]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  The function of microglia during progression of Alzheimer\u2019s 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\n                  <jats:italic>Cst7<\/jats:italic>\n                  locus (\n                  <jats:italic>Cst7<\/jats:italic>\n                  <jats:sup>DD-Cre<\/jats:sup>\n                  ) 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.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>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.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>DAMs represent a subset of plaque associated microglia (PAMs), and DAM expression increases with disease progression.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Spatial transcriptomic analyses reveal that DAMs have higher expression of disease and inflammatory genes compared to other PAMs.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.18.613773","type":"posted-content","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T15:55:13Z","timestamp":1726761313000},"source":"Crossref","is-referenced-by-count":0,"title":["Generation of an inducible destabilized-domain Cre mouse line to target disease associated microglia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9062-8672","authenticated-orcid":false,"given":"Caden 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Inman","family":"Tsourmas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8577-4763","authenticated-orcid":false,"given":"Shimako","family":"Kawauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3762-2746","authenticated-orcid":false,"given":"Vivek","family":"Swarup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-9501","authenticated-orcid":false,"given":"Grant R.","family":"MacGregor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim 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