The Macrophage-Specific Promoter mfap4 Allows Live, Long-Term Analysis of Macrophage Behavior during Mycobacterial Infection in Zebrafish

• Published in: PloS one Vol. 10; no. 10; p. e0138949
• Main Authors: Walton, Eric M, Cronan, Mark R, Beerman, Rebecca W, Tobin, David M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.10.2015; Public Library of Science (PLoS)
• Subjects: Animals; Animals, Genetically Modified - genetics; Animals, Genetically Modified - microbiology; Artificial chromosomes; Bacterial infections; Cell Lineage - genetics; Cloning; Danio rerio; Deoxyribonucleic acid; Disease Models, Animal; DNA; Gene expression; Genetic engineering; Genetics; Genomes; Health aspects; Host-Pathogen Interactions - genetics; Immune system; Immunity, Innate - genetics; Immunology; Infection; Infections; Labeling; Labelling; Larva - genetics; Larva - microbiology; Macrophages; Macrophages - microbiology; Mammals; Microorganisms; Mycobacterium Infections - genetics; Mycobacterium Infections - microbiology; Mycobacterium marinum; Mycobacterium marinum - pathogenicity; Neutrophils; Pathogenesis; Promoter Regions, Genetic - genetics; Proteins; Rodents; Salmonella; Salmonella typhimurium - pathogenicity; Transcription; Transgenes - genetics; Zebrafish; Zebrafish - genetics; Zebrafish - microbiology; Zebrafish Proteins - genetics; North Carolina; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138949

Transgenic labeling of innate immune cell lineages within the larval zebrafish allows for real-time, in vivo analyses of microbial pathogenesis within a vertebrate host. To date, labeling of zebrafish macrophages has been relatively limited, with the most specific expression coming from the mpeg1 promoter. However, mpeg1 transcription at both endogenous and transgenic loci becomes attenuated in the presence of intracellular pathogens, including Salmonella typhimurium and Mycobacterium marinum. Here, we describe mfap4 as a macrophage-specific promoter capable of producing transgenic lines in which transgene expression within larval macrophages remains stable throughout several days of infection. Additionally, we have developed a novel macrophage-specific Cre transgenic line under the control of mfap4, enabling macrophage-specific expression using existing floxed transgenic lines. These tools enrich the repertoire of transgenic lines and promoters available for studying zebrafish macrophage dynamics during infection and inflammation and add flexibility to the design of future macrophage-specific transgenic lines.