Characterization of the non-functional Fas ligand of gld mice

Hahne, Michael ; Peitsch, Manuel C. ; Irmler, Martin ; Schröter, Michael ; Lowin, Bente ; Rousseau, Marga ; Bron, Claude ; Renno, Toufic ; French, Lars ; Tschopp, Jürg

In: International Immunology, 1995, vol. 7, no. 9, p. 1381-1386

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    Summary
    Mice homozygous for either the gld or Ipr mutation develop autoimmune diseases and progressive lymphadenopathy. The Ipr mutation Is characterized by the absence of unctional Fas, whereas gld mice exhibit an inactive FasL due to a point mutation proximal to the extracellular C-terminus. The structural repercussions of this amino acid substitution remain unknown. Here we report that FasL Is expressed at similar levels on the surface of activated T lymphocytes from gld and wild-type mice. Using a polyclonal anti-FasL antibody, Indistinguishable amounts of a 40 kDa protein are detected In both gld and wild-type splenocytes. The molecular model of FasL, based on the known structure of TNF-α, predicts that the Phe→Leu gld mutation is located at the protomer interface which Is close to the FasR Interaction site. We conclude that the gld mutation allows normal FasL biosynthesis, surface expression and ollgomerlzatlon, but induces structural alterations to the Fas binding region leading to the phenotypic changes observed