title: Inactivation of the F4/80 glycoprotein in the mouse germ line.
abstract: Macrophages play a crucial role in the defense against pathogens. Distinct macrophage populations can be defined by the expression of restricted cell surface proteins. Resident tissue macrophages, encompassing Kupffer cells of the liver and red pulp macrophages of the spleen, characteristically express the F4/80 molecule, a cell surface glycoprotein related to the seven transmembrane-spanning family of hormone receptors. In this study, gene targeting was used to simultaneously inactivate the F4/80 molecule in the germ line of the mouse and to produce a mouse line that expresses the Cre recombinase under the direct control of the F4/80 promoter (F4/80-Cre knock-in). F4/80-deficient mice are healthy and fertile. Macrophage populations in tissues can develop in the absence of F4/80 expression. Functional analysis revealed that the generation of T-cell-independent B-cell responses and macrophage antimicrobial defense after infection with Listeria monocytogenes are not impaired in the absence of F4/80. Interestingly, tissues of F4/80-deficient mice could not be labeled with anti-BM8, another macrophage subset-specific marker with hitherto undefined molecular antigenic structure. Recombinant expression of a F4/80 cDNA in heterologous cells confirmed this observation, indicating that the targets recognized by the F4/80 and BM8 monoclonal antibodies are identical.
authors.affiliation: Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, D-81675 Munich, Germany.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Schaller
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Macfarlane
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Rupec
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McKnight
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D018390:Gene Targeting; D005838:Genotype; D005854:Germ Cells / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D014764:Viral Proteins; C036763:monocyte-macrophage differentiation antigen; D000072000:NF-KappaB Inhibitor alpha; C045073:Cre recombinase; D019426:Integrases