DEVELOPMENT OF A MOUSE MODEL FOR STUDYING IN-VIVO T-CELL RECEPTOR MUTATIONS

An experimental system was established to study in vivo T-cell recepto r alpha beta (TCR) mutations in murine CD4(+) T-lymphocytes. The frequ ency of TCR-defective mutant T-cells that have the CD3(-)3(+) surface phenotype, was measured using two-color flow cytometry of splenic T-ce lls passed through nylon wool, The spontaneous TCR mutant frequency (M F) in BALB/c mice (2.3 X 10(-4)) was significantly lower than the freq uencies of C57BL/6 (4.0 x 10(-4)) and C3H/He (4.2 X 10(-4)) mice. The general trend of the TCR MF started to increase at 3 days after whole- body X-irradiation, reached a peak level at 2-3 weeks, and then gradua lly decreased with a half-life of about 2 weeks. To analyze how the do se responses for each strain of mouse differed 2 weeks after X-irradia tion, the TCR MF dose responses were fitted to a linear-quadratic or a quadratic curve. The coefficients of the quadratic terms in both mode ls for BALB/c mice were significantly higher than those for the other two strains. These findings suggest that some genetic factor(s) may co ntrol the susceptibility of somatic genes to both spontaneous and radi ation-induced mutagenesis. Establishing an animal model for in vivo TC R mutations will contribute to the clarification of certain unresolved aspects of TCR mutagenesis in humans and will further advance knowled ge of screening for environmental mutagens. (C) 1997 Elsevier Science B.V.