Transnuclear mice with predefined T cell receptor specificities against Toxoplasma gondii obtained via SCNT.
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.
Kirak
Oktay
O
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. kirak@wi.mit.edu
Frickel
Eva-Maria
EM
Grotenbreg
Gijsbert M
GM
Suh
Heikyung
H
Jaenisch
Rudolf
R
Ploegh
Hidde L
HL
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D053595:Embryonic Stem Cells; D018984:Epitopes, T-Lymphocyte; D005260:Female; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D053652:Nuclear Transfer Techniques; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D015800:Protozoan Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta