Defective TCR expression in transgenic mice constructed using cDNA-based α- and β-chain genes under the control of heterologous regulatory elements
Defective TCR expression in transgenic mice constructed using cDNA-based α- and β-chain genes under the control of heterologous regulatory elements
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DOI：
10.1046/j.1440-1711.1998.00709.x
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发表时间：
1998-02-01
影响因子：
4
通讯作者：
Carbone, FR
中科院分区：
文献类型：
--
作者：
Barnden, MJ;Allison, J;Carbone, FR
我们描述了卵白蛋白（OVA）特异性，MHC ii类限制性α β T细胞受体（TCR）转基因小鼠的产生。产生这些转基因小鼠的最初尝试利用异源调控元件来驱动编码TCR分离的α链和β链的cDNA基因的表达。出乎意料的是，携带转基因α β TCR的T细胞未能从这些小鼠的胸腺中出现，尽管转基因确实改变了内源性TCR的表达。然而，随后对该方法进行修改，使TCR β链在其天然调控元件的控制下表达，产生了外周T细胞表达转基因TCR并能够抗原依赖性增殖的小鼠。这些结果表明，成功生成MHC ii类受限、ova特异性的α - β TCR转基因小鼠依赖于结合cDNA和基因组dna构建体来表达TCR的α链和β链。
We describe the generation of ovalbumin (OVA)-specific, MHC class II-restricted alpha beta T cell receptor (TCR) transgenic mice. Initial attempts at generating these transgenic mice utilized heterologous regulatory elements to drive the expression of cDNA genes encoding the separate alpha- and beta-chains of the TCR. Unexpectedly, T cells bearing the transgenic alpha beta TCR failed to emerge from the thymus in these mice, although the transgenes did modify endogenous TCR expression. However, subsequent modification of the approach which enabled expression of the TCR beta-chain under the control of its natural regulatory elements generated mice whose peripheral T cells expressed the transgenic TCR and were capable of antigen-dependent proliferation. These results show that successful generation of MHC class II-restricted, OVA-specific alpha beta TCR transgenic mice was dependent upon combining cDNA- and genomic DNA-based constructs for expression of the respective alpha- and beta-chains of the TCR.