Development of a mouse model for studying in vivo T-cell receptor mutations

An experimental system was established to study in vivo T-cell receptor alpha beta (TCR) mutations in murine CD4+ T-lymphocytes. The frequency of TCR-defective mutant T-cells that have the CD3-4+ surface phenotype, was measured using two-color flow cytometry of splenic T-cells passed through nylon wool. The spontaneous TCR mutant frequency (MF) in BALB/c mice (2.3 x 10(-4)) was significantly lower than the frequencies 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 gradually decreased with a half-life of about 2 weeks. To analyze how the dose responses for each strain of mouse differed 2 weeks after X-irradiation, the TCR MF dose responses were fitted to a linear-quadratic or a quadratic curve. The coefficients of the quadratic terms in both models for BALB/c mice were significantly higher than those for the other two strains. These findings suggest that some genetic factor(s) may control the susceptibility of somatic genes to both spontaneous and radiation-induced mutagenesis. Establishing an animal model for in vivo TCR mutations will contribute to the clarification of certain unresolved aspects of TCR mutagenesis in humans and will further advance knowledge of screening for environmental mutagens.