Functional Fas (Cd95/Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to gamma-radiation-induced thymic lymphoma.
The Fas death receptor is a cell surface molecule involved in apoptosis as well as in proliferative or activating signals of many cells types, including T lymphocytes. Using quantitative real-time reverse transcription-PCR analysis, we confirm that expression of this gene is scarcely perceptible in thymic lymphomas induced by gamma-irradiation in C57BL/6J mice. Notably, we also demonstrate for the first time that Fas expression is significantly upregulated in vivo both after single high dose of radiation and in thymic lymphoma-free mice. In addition, we determined its levels of expression in five mouse strains exhibiting different degrees of susceptibility (SPRET/Ei, SEG/Pas, BALB/cJ, C57BL/6J and RF/J). Interestingly, we found the highest levels of expression in SPRET/Ei and SEG/Pas strains (both derived from the Mus spretus species), which are known to have the most resistant phenotype, and the lowest levels in the most susceptible strains C57BL/6J and RF/J. DNA sequencing of the Fas promoter in all five strains showed many polymorphisms that can be classified into three functional haplotypes by using luciferase assays: (1) C57BL/6J and RF/J, (2) BALB/cJ and (3) SPRET/Ei and SEG/Pas. Promoter activities in response to single high doses of radiation correlated well with the levels of Fas expression and are consistent with the degree of strain susceptibility.
Villa-Morales
M
M
Laboratorio de Genética Molecular Humana, Departamento de Biología, Universidad Autónoma de Madrid, Madrid, Spain.
Santos
J
J
Fernández-Piqueras
J
J
D000818:Animals; D001483:Base Sequence; D004247:DNA; D005720:Gamma Rays; D020022:Genetic Predisposition to Disease; D006801:Humans; D019169:Jurkat Cells; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013953:Thymus Neoplasms / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics*
D019014:fas Receptor; D004247:DNA