THE MOUSE FAS-LIGAND GENE IS MUTATED IN GLD MICE AND IS PART OF A TNFFAMILY GENE-CLUSTER

The gene for the mouse Fas ligand was cloned and its chromosomal posit ion determined. Fasl was tightly linked to gld (no crossovers in 567 m eiotic events) on mouse chromosome 1 and closely linked with a novel m ember of the same TNF family of ligands, the Ox40 ligand (Ox40l, 1 cro ssover in 567 meiotic events). Southern blot analysis did not reveal a ny difference between the Fasl gene from gld and wild-type mice and le vels of Fasl mRNA transcripts were similar in PMA and ionomycin induce d wild-type and coisogenic gld T cells. Sequence analysis of the gld g ene indicated a single amino acid change(Phe Leu) in the COOH terminal portion of this type II transmembrane protein, and COS cells transfec ted with Fasl cDNA from gld mice failed to induce apoptosis of pas-exp ressing target cells. Thus, the data demonstrate that the gld phenotyp e is the result of a point mutation in the Fasl gene and that Fasl is part of a complex of ligands structurally related to TNF mapping withi n a small region of mouse chromosome 1.