Open AccessSex‐limited protein: in vitro and in vivo functions
Author(s) -
Frank J. Beurskens,
J D M Kuenen,
F. M. A. Hofhuis,
Ad C. Fluit,
Diane M. Robins,
Hans van Dijk
Publication year - 1999
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1999.00907.x
Subject(s) - transgene , biology , genetically modified mouse , immunology , complement system , in vivo , gene knockin , gene isoform , alternative complement pathway , microbiology and biotechnology , genetics , gene , immune system
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 (CH 50 and AP 50 levels, respectively). Slp‐transgenic C57Bl/6J mice showed enhanced CH 50 , but normal AP 50 levels when compared with non‐transgenic littermates. To discover a possible protective role for Slp in spontaneous systemic lupus erythematosus (SLE) in NZB×NZW (NZB×W) 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 NZB×W 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.