Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 75, Issue 4, Pages 612-623Publisher
WILEY
DOI: 10.1189/jlb.0903442
Keywords
depletion; c-fms; dendritic cell; GFP; peritoneal adhesion; Yersinia pestis
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Funding
- NHLBI NIH HHS [HL69459, HL57399] Funding Source: Medline
- NIAID NIH HHS [5T32AI049795] Funding Source: Medline
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Transgenic mice expressing an inducible suicide gene, which allows systemic and reversible elimination of macrophages, were developed. A macrophage-specific c-fins 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 he useful in investigating the role of macrophages and DC.
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