Transnuclear Mice with Predefined T Cell Receptor Specificities Against Toxoplasma gondii Obtained via SCNT

被引:46
作者
Kirak, Oktay [1 ]
Frickel, Eva-Maria [1 ]
Grotenbreg, Gijsbert M. [1 ]
Suh, Heikyung [1 ]
Jaenisch, Rudolf [1 ,2 ]
Ploegh, Hidde L. [1 ,2 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02142 USA
关键词
MOUSE CLONING; NEGATIVE SELECTION; NUCLEAR TRANSFER; TCR EXPRESSION; TRICHOSTATIN-A; IMMUNITY; RESPONSES; GENES;
D O I
10.1126/science.1178590
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mice that are transgenic for rearranged antigen-specific T cell receptors (TCRs) are essential tools to study T cell development and function. Such TCRs are usually isolated from the relevant T cells after long-term culture, often after repeated antigen stimulation, which unavoidably skews the T cell population used. Random genomic integration of the TCR alpha and beta chain and expression from nonendogenous promoters represent additional drawbacks of transgenics. Using epigenetic reprogramming via somatic cell nuclear transfer, we demonstrated that T cells with predefined specificities against Toxoplasma gondii can be used to generate mouse models that express the TCR from their endogenous loci, without experimentally introduced genetic modification. The relative ease and speed with which such transnuclear models can be obtained holds promise for the construction of other disease models.
引用
收藏
页码:243 / 248
页数:6
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