1. ¹Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
2. ²State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, PR China
3. ³Evanston Northwestern Healthcare Research Institute, Northwestern University, Evanston, IL, USA

Correspondence: Dr F Huang, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, #138 Yi Xue Yuan Road, Shanghai 200032, PR China. E-mail: huangf@shmu.edu.cn; Dr H Gu, Department of Microbiology, College of Physicians and Surgeons, Columbia University, HHSC Rm6-611, 701 West 168th street, New York, NY 10032, USA. E-mail: hg2065@columbia.edu

Received 17 August 2007; Revised 20 January 2008; Accepted 18 February 2008; Published online 8 April 2008.

Abstract

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.