Cited by 307Animal Genetics and ReproductionPhagocytosis and Immune RegulationImmunotoxicology and immune responses

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Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene

Burnett, Sandra H, Kershen, Edward J, Zhang, Jiayou, Zeng, Li, Straley, Susan C, Kaplan, Alan M, Cohen, Donald A·2004·Journal of Leukocyte Biology

DOI 10.1189/jlb.0903442

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Abstract

Transgenic mice expressing an inducible suicide gene, which allows systemic and reversible elimination of macrophages, were developed. A macrophage-specific c-fms promoter was used to express enhanced green fluorescent protein and a drug-inducible suicide gene that leads to Fas-mediated apoptosis in resting and cycling cells of the macrophage lineage. Transgenic mice were fertile, of normal weight, and showed no abnormal phenotype before drug exposure. The transgene was expressed constitutively in macrophages and dendritic cells (DC) but not significantly in T cells or B cells. Induction of the suicide gene led to depletion of 70–95% of macrophages and DC in nearly all tissues examined. Depletion reduced the ability to clear bacteria from the blood and led to increased bacterial growth in the liver. Depleted mice displayed several abnormalities, including splenomegaly, lymphadenopathy, thymic atrophy, extramedullary hematopoiesis, and development of peritoneal adhesions. This new, transgenic line will be useful in investigating the role of macrophages and DC.

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Self-citation

Authors: Burnett, S. H., Kershen, E. J., Zhang, J., Zeng, L., Straley, S. C., Kaplan, A. M., & Cohen, D. A.
Affiliations: University of Kentucky (US)
Corresponding author: Cohen, Donald A
ORCID: Zhang, Jiayou
Zeng, Li
Venue: Journal of Leukocyte Biology
Publisher: Oxford University Press (OUP)
Published: 2004-01-14
Volume: 75
Issue: 4
Pages: 612-623
ISSN: 0741-5400 (ISSN-L)
1938-3673
DOI: 10.1189/jlb.0903442
OpenAlex: W2163279811
Cited by: 307
References: 44
Citations by year: 2026: 7 · 2025: 10 · 2024: 21 · 2023: 17 · 2022: 15 · 2021: 17 · 2020: 18 · 2019: 12 · 2018: 17 · 2017: 20 · 2016: 13 · 2015: 22 · 2014: 21 · 2013: 18 · 2012: 11
FWCI: 3.20
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: Journal of Leukocyte Biology (publishedVersion)
PubMed (publishedVersion)
Funders: NIH (HL69459, HL57399, 5T32AI049795)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Keywords: macrophage depletion, dendritic cells, bacterial clearance, splenomegaly, lymphadenopathy, thymic atrophy, extramedullary hematopoiesis, peritoneal adhesions, transgenic mice
MeSH terms: Animals, Bacterial Infections, Cell Count, Cells, Cultured, Dendritic Cells, Disease Models, Animal, Immunity, Cellular, Luminescent Proteins, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Promoter Regions, Genetic, Receptor, Macrophage Colony-Stimulating Factor, Tacrolimus, Apoptosis, Receptors, Nerve Growth Factor, fas Receptor, Dimerization, Tacrolimus Binding Proteins, Genes, Transgenic, Suicide, Green Fluorescent Proteins, Mice

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Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene

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