| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
Rit1/Bcl11b is a haploinsufficient tumor suppressor gene and plays an essential role inαβT cell development. Bcl11b knockout mice exhibit a developmental block at DN stage and do not generate DP thymocytes. On the other hand, Bcl11b heterozygous mice appear to be normal but show retardation of thymocyte development in embryos. This suggests dose-dependency of Bcl11b function in differentiation of thymocytes. To analyze this dose-dependency, we generated mice carrying the hypomorphic allele of Bcl11b by mutagen treatment conducted in RIKEN large scale ENU Mutagenesis Program. Among six such mutants analyzed, one(1891mut) carries one-base substitution leading to a missense mutation. Here, we show a developmental impairment at the CD69+TCRbhigh transitional stage of positive selection caused by the presence of 1891mut allele. As a result, development of CD8SP cells, but not of CD4SP, was reduced in 1891mut/+mice. This reduction was more severe in KO/+mice. Our data suggest that differentiation of CD8 lineage T cells is controlled by Bcl11b and its processing level is affected by or dependent on the Bcl11b activity.
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