Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene (original) (raw)

Journal Article

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Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

,

Lexington

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Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

,

Lexington

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Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

,

Lexington

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,

Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

,

Lexington

Search for other works by this author on:

,

Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

,

Lexington

Search for other works by this author on:

,

Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

,

Lexington

Search for other works by this author on:

Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

,

Lexington

Correspondence: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, Room MS419, Lexington, Kentucky 40536-0084. E-mail: dcohen@pop.uky.edu

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Received:

24 September 2003

Revision received:

16 December 2003

Accepted:

18 December 2003

Published:

14 January 2004

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Sandra H Burnett, Edward J Kershen, Jiayou Zhang, Li Zeng, Susan C Straley, Alan M Kaplan, Donald A Cohen, Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene, Journal of Leukocyte Biology, Volume 75, Issue 4, April 2004, Pages 612–623, https://doi.org/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.

© 2004 Society for Leukocyte Biology

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