title: Mouse lymphomas caused by an intron-splicing donor site deletion of the FasL gene.
abstract: A spontaneous lymphoma was detected in mice, which was caused by a recessive autosomal mutation. The genetic basis was revealed to be a 5-bp deletion at the splicing donor site of the first intron of the FasL gene, resulting in aberrant transcripts coding for non-functional proteins. This mutation of the FasL gene caused development of lymphoma in all four mouse genetic backgrounds tested and the lymphoma was characterized by an expansion of leucocytes that were TCR+CD3+B220+CD19-CD4-CD8-. Accordingly, severe splenomegaly developed in the mutant mice. Interestingly, thymic hyperplasia was observed in mutant mice at later stages. These results underscore the functional importance of the splicing donor site in the function of the FasL gene and provide an independent evidence for a role of FasL in normal development of lymophocytes. The mutant mice offer another genetically defined mouse model for further studies of the role and mechanism of action of FasL.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: Cheng-Chun
authors.initials: CC
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zeng
authors.forename: Le-Ann
authors.initials: LA
authors.lastname: Hwang
authors.forename: Ke
authors.initials: K
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Hwee Chien
authors.initials: HC
authors.lastname: Liew
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D020022:Genetic Predisposition to Disease; D007438:Introns; D007962:Leukocytes / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D048069:Tumor Necrosis Factors / Q000235:genetics*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D019014:fas Receptor