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Publication : Functional Fas (Cd95/Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to gamma-radiation-induced thymic lymphoma.

First Author  Villa-Morales M Year  2006
Journal  Oncogene Volume  25
Issue  14 Pages  2022-9
PubMed ID  16301997 Mgi Jnum  J:107261
Mgi Id  MGI:3620475 Doi  10.1038/sj.onc.1209234
Citation  Villa-Morales M, et al. (2006) Functional Fas (Cd95/Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to gamma-radiation-induced thymic lymphoma. Oncogene 25(14):2022-9
abstractText  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.
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