The V-J recombination of T cell receptor-gamma genes is blocked in interleukin-7 receptor-deficient mice.

The V-J recombination of T cell receptor-gamma genes is blocked in interleukin-7 receptor-deficient mice.
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DOI:
10.1084/jem.184.6.2423
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发表时间:
1996-12-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Ikuta K
Ikuta K
中科院分区:
其他
文献类型:
--
作者:
Maki K;Sunaga S;Ikuta K

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IL-7R缺陷小鼠早期淋巴细胞的增殖严重受损,缺乏γδT细胞。为了阐明IL-7R在γδT细胞发育中的作用,我们分析了IL-7R缺陷小鼠胸腺中TcR-α,β,γ和δ基因的重排。用Jγ1探针进行Southern杂交分析表明,在对照小鼠中,70%以上的Jγ1和Jγ2等位基因重组形成不同的Vγ1.2-Jγ2和Vγ2-Jγ1片段。相反,在突变小鼠中没有检测到这种重组。TcR-α,β和δ基因座的重排在对照和突变小鼠中观察到类似的重排。聚合酶链式反应分析表明,所有V-γ基因的V-J重组在突变小鼠中受到严重阻碍。在对照和突变胸腺中均检测到RAG-1、RAG-2、Ku-80和末端脱氧核苷酸转移酶(TDT)基因的mRNA,提示常见重组机制的表达不受影响。这些数据表明,在IL-7R缺陷小鼠中,TCRγ基因的V-J重组被特异性地阻断,并提示对TCRγ基因重排存在高度特异性的调节。
IL-7R-deficient mice have severely impaired expansion of early lymphocytes and lack γδ T cells. To elucidate the role of IL-7R on γδ T cell development, we analyzed the rearrangements of TCR-α, β, γ, and δ genes in the thymus of the IL-7R-deficient mice. Southern blot analysis with a Jγ1 probe revealed that more than 70% of Jγ1 and Jγ2 alleles are recombined to form distinct Vγ1.2–Jγ2 and Vγ2–Jγ1 fragments in control mice. On the contrary, no such recombination was detected in the mutant mice. The rearrangements in the TCR-α, β, and δ loci were comparably observed in control and mutant mice. PCR analysis indicated that the V–J recombination of all the Vγ genes is severely hampered in the mutant mice. The mRNA of RAG-1, RAG-2, Ku-80, and terminal deoxynucleotidyl transferase (TdT) genes was equally detected between control and mutant thymi, suggesting that the expression of common recombination machinery is not affected. These data demonstrated that the V–J recombination of the TCR γ genes is specifically blocked in the IL-7R-deficient mice and suggested the presence of highly specific regulation for TCR γ gene rearrangement.