title: Complete loss of Fas ligand gene causes massive lymphoproliferation and early death, indicating a residual activity of gld allele.
abstract: To investigate the in vivo function of Fas ligand (FasL), we produced a mouse strain with a FasL gene flanked by loxP sequences. Mice with homozygous floxed FasL gene showed no obvious abnormalities. However, germline deletion of the FasL gene, obtained after mating with mice expressing ubiquitous Cre recombinase, resulted in an unexpectedly severe phenotype. FasL(-/-) mice exhibited an extreme splenomegaly and lymphadenopathy associated with lymphocytic infiltration into multiple organs and autoimmune disease. This severe phenotype led to the premature death at 4 mo of age of >50% of the homozygous mice. It stands in sharp contrast with the milder disease observed in gld (generalized lymphoproliferative disease) mice, indicating that the FasL allele of these mice encodes a protein still able to bind, albeit at a very low level, the Fas receptor.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 580, Hôpital Necker, Paris, France. karray@necker.fr
authors.forename: Saoussen
authors.initials: S
authors.lastname: Karray
authors.forename: Chantal
authors.initials: C
authors.lastname: Kress
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cuvellier
authors.forename: Catherine
authors.initials: C
authors.lastname: Hue-Beauvais
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
authors.forename: Charles
authors.initials: C
authors.lastname: Babinet
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lévi-Strauss
mesh_terms: D000483:Alleles; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D053222:Fas Ligand Protein; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing / Q000276:immunology*; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006942:Hypergammaglobulinemia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008024:Ligands; D008099:Liver / Q000276:immunology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D017493:Leukocyte Common Antigens