title: Functional significance of the Fas molecule in naive lymphocytes.
abstract: The Fas molecule mediates apoptotic signal in many cell types. Mouse mutations (lpr, lprcg, gld), which impair the function of Fas, cause spontaneous autoimmune disease. We generated Fas-deficient (Fas-/-) mice by homologous recombination. In embryonic stem cells Fas-/- mice developed lpr-like disease, confirming that the abnormality of Fas is causal in the lpr phenotype. We also made Fas-/- chimeric mice composed of a mixture of Fas+/+ and Fas-/- cells. The chimeric mice also showed the lpr phenotype. In Fas-/-, chimeric mice, the Fas-deficient population expanded progressively among mature T and B lymphocytes. The expansion of Fas-deficient lymphocytes occurred at the naive, pre-primed, lymphocyte stage. These results suggest that the Fas molecule functions not only after antigenic stimulation, as previously hypothesized, but also at the naive lymphocyte stage.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: S
authors.initials: S
authors.lastname: Senju
authors.forename: I
authors.initials: I
authors.lastname: Negishi
authors.forename: N
authors.initials: N
authors.lastname: Motoyama
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: P J
authors.initials: PJ
authors.lastname: Lucas
authors.forename: S
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Yonehara
authors.forename: D Y
authors.initials: DY
authors.lastname: Loh
mesh_terms: D000818:Animals; D001483:Base Sequence; D002678:Chimera; D003001:Cloning, Molecular; D015870:Gene Expression; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*
chemical_list: D019014:fas Receptor