Do mouse strains have Fas ligands with different activity?

Details

Fas ligand (FasL) belongs to the tumor necrosis factor family and induces apoptosis in target cells bearing Fas (CD95). Researchers generated several monoclonal antibodies that react with mouse FasL (mFasL) and characterized their functional properties.

One antibody, K10, reacted specifically with mFasL from C57BL/6 (B6) mice but not BALB/c mice, as assessed by surface staining and blocking the cytotoxic activities of mFasL transfectants; this suggested a polymorphism in mFasL. Sequence analysis of mFasL cDNA from several strains found that BALB/c and DBA/2 mice had three nucleotide differences from the known B6 and C3H sequences, resulting in two extracellular amino acid substitutions: Thr-184 to Ala-184 and Glu-218 to Gly-218. K10 reactivity analysis and genotyping by PCR-restriction fragment length polymorphism separated the inbred mice into two allotypes: mFasL.1 (B6, C3H, MRL, SJL, NOD and NZB, NZW) and mFasL.2 (BALB/c, DBA/1 and DBA/2).

COS7 cells expressing BALB/c FasL lysed Fas-bearing target cells more efficiently than those expressing B6 FasL. A BALB/c-derived CD8-FasL fusion protein, composed of the extracellular domains of human CD8alpha and mFasL, also had ninefold higher specific activity than B6-derived CD8-FasL. The researchers suggest that the Fas/FasL system works more effectively in mFasL.2 mice than in mFasL.1 mice.