title: Genetic analysis of innate resistance to mouse cytomegalovirus (MCMV).
abstract: Innate immunity is inherited and is, therefore, particularly susceptible to analysis by classical genetic methods. The 'phenotype first' approach has already revealed the principal receptors of the innate immune system as well as several essential signalling intermediates. It has recently emerged that innate resistance to mouse cytomegalovirus (MCMV) infection depends upon a large number of host genes with non-redundant functions; hence, random germline mutagenesis frequently causes susceptibility to this pathogen. Approximately one in 30 pedigrees derived from N-ethyl-N-nitrosourea-mutagenised progenitors bears a recessive mutation that disrupts resistance to MCMV. Moreover, many of the genes required for resistance to MCMV will undoubtedly prove to have broad roles in immunity, creating resistance to many other microbes. The forward genetics approach offers an excellent opportunity to identify many of the key components of the innate immune system.
authors.affiliation: The Scripps Research Institute, 10550 N. Torrey Pines Road, IMM-31, La Jolla, CA 92037, USA. bruce@scripps.edu
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.forename: Philippe
authors.initials: P
authors.lastname: Georgel
authors.forename: Sophie
authors.initials: S
authors.lastname: Rutschmann
authors.forename: Zhengfan
authors.initials: Z
authors.lastname: Jiang
authors.forename: Ben
authors.initials: B
authors.lastname: Croker
authors.forename: Karine
authors.initials: K
authors.lastname: Crozat
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D003600:Cytosol / Q000378:metabolism; D005038:Ethylnitrosourea / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D016678:Genome; D018095:Germ-Line Mutation; D007113:Immunity, Innate; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D018146:Muromegalovirus / Q000378:metabolism*; D016296:Mutagenesis; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation
chemical_list: D016207:Cytokines; D005038:Ethylnitrosourea