T-CELL RECEPTOR (TCR) BETA-CHAIN TRANSGENIC MICE - STUDIES ON ALLELIC EXCLUSION AND ON THE TCR+ GAMMA-DELTA-POPULATION

T-CELL RECEPTOR (TCR) BETA-CHAIN TRANSGENIC MICE - STUDIES ON ALLELIC EXCLUSION AND ON THE TCR+ GAMMA-DELTA-POPULATION
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DOI:
10.1002/eji.1830200227
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发表时间:
1990-02-01
影响因子:
5.4
通讯作者:
HENGARTNER, H
HENGARTNER, H
中科院分区:
医学3区
文献类型:
--
作者:
PIRCHER, H;OHASHI, P;HENGARTNER, H

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为了研究TCR基因的等位基因排斥性,我们分析了两种类型的TCRβ。转基因小鼠。来自两种类型小鼠的T细胞含有类似数量的转基因RNA转录本;然而,转基因β基因的表面表达。与I型相比,II型转基因小鼠的链显著减少,在I型转基因小鼠中,生产性重排和内源性TCR.beta的表达。基因被抑制,而在II型小鼠的T细胞上,无论是转基因的还是内源性的TCR.beta。链在同一细胞表面表达。这些发现表明,β基因中TCR基因的等位基因排斥。转基因小鼠取决于胸腺发育过程中转基因表达的数量和/或开始。此外,TCR.伽马。在I型转基因动物中,携带TCRγ/β的双阴性胸腺细胞的重排和数量减少了五倍。然而,V.Gamma。用法和γ/β+树突状表皮细胞种群显示正常。核糖核酸酶保护分析进一步揭示了转基因TCR.beta的低水平。链转录本以TCR+伽马/增量表示。CD4-CD8-胸腺细胞。这些结果表明,测试版。转基因只在数量上影响伽马/增量。T细胞室,并支持伽马/增量的独立性。人口。
To study allelic exclusion of TcR genes we analyzed two types (I and II) of TcR .beta. transgenic mice. T cells derived from both types of mice contained similar amounts of transgenic RNA transcripts; however, surface expression of the transgenic .beta. chain was drastically reduced in type II compared to type I. In type I transgenic mice, productive rearrangements and expression of endogenous TcR .beta. genes were suppressed whereas on T cells of type II mice, both transgenic and endogenous TcR .beta. chains were expressed on the surface of the same cell. These findings suggest that allelic exclusion of TcR genes in .beta. transgenic mice depends on amount and/or onset of transgene expression during thymic development. Furthermore, TcR .gamma. rearrangements and the population of TcR .gamma./.delta.-bearing double-negative CD4-CD8- thymocytes were reduced fivefold in type I transgenic animals. However, the V.gamma. usage and the .gamma./.delta.+ dendritic epidermal cell populations appeared normal. RNase protection analysis further revealed low levels of trangenic TcR .beta. chain transcripts in TcR+ .gamma./.delta. CD4-CD8- thymocytes. These results suggest that the .beta. transgene only quantitatively influences the .gamma./.delta. T cell compartment, and supports the independence of the .gamma./.delta. population.