| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
The ATM deficient mouse exhibits fewer CD4 and CD8 single positive T-cells due to a failure to develop from the CD4+CD8+ double positive phase to the SP phase. Although the occurrence of chromosome 14 translocations involving TCR alpha gene in ATM-deficient lymphomas suggest that these are early events in T-cell development, an thorough analysis focusing on early T-cell development has never been performed. We demonstrate that ATM deficient T cell are perturbed in passing through the beta or gamma/delta selection checkpoint, leading in part to the developmental failure of T-cells. Detailed karyotype analysis employing in vitro thymocyte development system revealed that RAG mediated TCR alpha/delta locus breaks occur and are left unrepaired during the troublesome beta or gamma/delta selection checkpoints. By getting through these selection checkpoints some of the clones with random or non-random chromosomal translocations involving TC Ralpha/delta locus are selected and accumulate.
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