{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:10:10Z","timestamp":1791688210121,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K08 NS102507\u201001A1"],"award-info":[{"award-number":["K08 NS102507\u201001A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24CA095823"],"award-info":[{"award-number":["R24CA095823"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000910","name":"Conrad N. Hilton Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000910","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The transgenic murine\n                      <jats:italic>Cre\/loxP<\/jats:italic>\n                      system is deployed to investigate the role of central nervous system (CNS) cell\u2010specific gene alterations in both healthy conditions and models of neurologic disease. The\n                      <jats:italic>Aldh1l1\u2010Cre\/ERT2<\/jats:italic>\n                      line is widely used to target astrocytes with high coverage and specificity within the CNS. Specificity outside the CNS, however, has not been well\u2010characterized, and Aldh1l1\u2010Cre\/ERT2\u2010mediated recombination within the spleen has been reported. In many CNS diseases, infiltrating immune cells from the periphery drive or regulate pathogenesis. We tested whether flox\u2010mediated recombination from Aldh1l1\u2010Cre\/ERT2 occurs in immune cells in addition to astrocytes and whether these cells traffic from the spleen into the spinal cord during experimental autoimmune encephalomyelitis (EAE), a model of CNS autoimmune disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two astrocyte\u2010targeted mouse lines were generated with the red fluorescent reporter, tdTomato, by crossing the Cre\u2010recombinase lines,\n                      <jats:italic>Tg(Aldh1l1\u2010Cre\/ERT2)1Khakh<\/jats:italic>\n                      and\n                      <jats:italic>Tg(Gfap\u2010Cre)73.12Mvs<\/jats:italic>\n                      , with the reporter line,\n                      <jats:italic>Gt(ROSA)26Sor<\/jats:italic>\n                      . Aldh1l1\u2010Cre\/ERT2 was activated with 5 days of intraperitoneal tamoxifen, whereas Gfap\u2010Cre was constitutively active. EAE was induced 2 weeks after tamoxifen, and then spleens and spinal cords were harvested and processed for flow cytometry at various time points after disease onset in EAE versus healthy controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In EAE, Aldh1l1\u2010Cre\/ERT2, but not Gfap\u2010Cre, induced multiple tdTomato\n                      <jats:sup>+<\/jats:sup>\n                      immune cell subpopulations in the spleen and spinal cord, including macrophages, monocytes, neutrophils, eosinophils, B cells, CD4\n                      <jats:sup>+<\/jats:sup>\n                      , and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Use of Aldh1l1\u2010Cre\/ERT2 should therefore account for recombination in both astrocytes and immune cells in disease models involving peripheral immune cell infiltration into the CNS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70239","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T01:30:37Z","timestamp":1738805437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Aldh1l1\u2010Cre\/ERT2 Drives Flox\u2010Mediated Recombination in Peripheral and CNS Infiltrating Immune Cells in Addition to Astrocytes During CNS Autoimmune Disease"],"prefix":"10.1002","volume":"15","author":[{"given":"Mario","family":"Amatruda","sequence":"first","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Turati","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1246-2857","authenticated-orcid":false,"given":"Jorge","family":"Villavicencio","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Immunotherapy Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-1223","authenticated-orcid":false,"given":"Graham","family":"Britton","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5391-9000","authenticated-orcid":false,"given":"Sam","family":"Horng","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York 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