title: Sex-limited protein: in vitro and in vivo functions.
abstract: Mouse complement component C4 exists in two isoforms, C4 and a protein with expression restricted to male animals called sex-limited protein (Slp). Although Slp is about 95% homologous to C4, it is generally believed to be non-functional, at least in conventional haemolytic complement assays. In a previous study, however, we showed that Slp is haemolytically active in a C1-inhibitor (C1INH)-regulated, EDTA-resistant mouse complement activation pathway. To study other possible implications of this finding, we generated constitutively expressing Slp-transgenic mice. The transgene was crossed into otherwise Slp-deficient C57Bl/6J and NZB mice. Members of the third backcross generation of C57Bl/6J mice were tested for functional Slp and classical and alternative complement pathway activities (CH50 and AP50 levels, respectively). Slp-transgenic C57Bl/6J mice showed enhanced CH50, but normal AP50 levels when compared with non-transgenic littermates. To discover a possible protective role for Slp in spontaneous systemic lupus erythematosus (SLE) in NZBxNZW (NZBxW) mice, the third backcross generation of Slp-transgenic NZB mice was mated with NZW mice and the development of SLE in the female offspring was followed. In these introductory experiments, Slp-transgenic NZBxW animals presented with a significantly extended life span. Our results imply that Slp is a mouse complement component with functions which partially resemble some of those of human C4A.
authors.affiliation: Eijkman-Winkler Institute for Microbiology, Infectious Diseases, and Inflammation, Utrecht University Hospital, Utrecht, The Netherlands. F.J.M.Beurskens@lab.azu.nl
authors.forename: F J
authors.initials: FJ
authors.lastname: Beurskens
authors.forename: J D
authors.initials: JD
authors.lastname: Kuenen
authors.forename: F
authors.initials: F
authors.lastname: Hofhuis
authors.forename: A C
authors.initials: AC
authors.lastname: Fluit
authors.forename: D M
authors.initials: DM
authors.lastname: Robins
authors.forename: H
authors.initials: H
authors.lastname: Van Dijk
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000276:immunology*; D003181:Complement C4 / Q000235:genetics / Q000378:metabolism*; D015941:Complement Hemolytic Activity Assay; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic
chemical_list: D001798:Blood Proteins; C018386:C4a protein, mouse; D003181:Complement C4