Sex-limited protein: in vitro and in vivo functions

Author:

BEURSKENS F J M1,KUENEN J D M1,HOFHUIS F2,FLUIT A C1,ROBINS D M3,VAN DIJK H1

Affiliation:

1. Eijkman-Winkler Institute for Microbiology, Infectious Diseases, and Inflammation

2. Department of Immunology, Utrecht University Hospital, Utrecht, The Netherlands

3. Department of Human Genetics, The University of Michigan, Ann Arbor, MI, USA

Abstract

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 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.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

Reference20 articles.

1. Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein;Stavenhagen;Mol Cell Biol,1987

2. A simple salting out procedure for extracting DNA from human nucleated cells;Miller;Nucleic Acids Res,1988

3. Sequence comparison of alleles of the fourth component of complement (C4) and sex-limited protein (Slp);Hemenway;Nucleic Acids Res,1986

4. Slp is an essential component of an EDTA-resistant activation pathway of mouse complement;Van den Berg;Proc Natl Acad Sci USA,1992

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