The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster.
The gene for the mouse Fas ligand was cloned and its chromosomal position determined. Fasl was tightly linked to gld (no crossovers in 567 meiotic events) on mouse chromosome 1 and closely linked with a novel member of the same TNF family of ligands, the Ox40 ligand (Ox40l, 1 crossover in 567 meiotic events). Southern blot analysis did not reveal any difference between the Fasl gene from gld and wild-type mice and levels of Fasl mRNA transcripts were similar in PMA and ionomycin induced wild-type and coisogenic gld T cells. Sequence analysis of the gld gene indicated a single amino acid change (Phe Leu) in the COOH terminal portion of this type II transmembrane protein, and COS cells transfected with Fasl cDNA from gld mice failed to induce apoptosis of Fas-expressing target cells. Thus, the data demonstrate that the gld phenotype 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 within a small region of mouse chromosome 1.
Lynch
D H
DH
Department of Immunobiology, Immunex Research and Development Corporation, Seattle, Washington 98101.
Watson
M L
ML
Alderson
M R
MR
Baum
P R
PR
Miller
R E
RE
Tough
T
T
Gibson
M
M
Davis-Smith
T
T
Smith
C A
CA
Hunter
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D053222:Fas Ligand Protein; D008040:Genetic Linkage; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D010641:Phenotype; D017354:Point Mutation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA