TM1 and TM2: two mutant alleles that are involved in the pre-TCR/TCR signaling

It has been shown that the transgene insertional mutations TM1 and TM2 constitute a genetic trait controlling thymocyte development. Here we conducted a detailed analysis of the impact of TM1 and TM2 double mutation on thymocyte development. We found that the hemizygous TM1 and TM2 double transgenic mice possessed much smaller thymi. Flow cytometric analysis revealed a severe blockage of T-cell development at the transition from DN3 to DN4 stage and pre-T-cell receptor (pre-TCR)/TCR signaling appeared to be impaired. We could not identify any known gene that was implicated in a similar function in the chromosomal regions 7E-F1 and 11B5-C, where TM1 and TM2 mutations were mapped to respectively. Thus, TM1 and TM2 mutations represent two novel alleles that define a genetic trait controlling DN3 thymocyte development, possibly through modulating the signals downstream of the pre-TCR.