标题：Exogenous Mtv-7 superantigen transgene expression in major histocompatibility complex class II I-E- mice reconstituted with embryonic stem cell-derived hematopoietic stem cells.
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1994
卷号：91
期号：3
页码：1138-1142
DOI：10.1073/pnas.91.3.1138
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Direct genetic manipulation of hematopoietic cells is limited by the lack of an established hematopoietic stem cell line. It has been demonstrated that embryonic stem (ES) cell<-->tetraploid embryos are completely ES cell-derived and that fetal liver (FL) cells from these embryos support hematopoiesis in lethally irradiated recipients. In this report, we demonstrate that FL cells from ES cell<-->tetraploid embryos support normal lymphopoiesis and T-cell repertoire development. Moreover, the introduction of the Mtv-7 superantigen transgene coding for minor lymphocyte stimulatory antigen 1 into murine hematopoietic cells via reconstitution with ES cell<-->tetraploid FL cells demonstrates that this method can effectively confer stable genetic changes into the hematopoietic tissues without going through the germ line. Long-term and secondary reconstitution with ES cell<-->tetraploid FL cells expressing the Mtv-7 superantigen transgene clonally deleted minor lymphocyte stimulatory antigen 1-reactive T-cell receptor V beta 6+, -8.1+, and -9+ T cells, but not V beta 7+ T cells, in H-2b (I-E-) mice. This model system will be extremely important for analyzing structure-function relationships of molecules involved in proliferation, differentiation, and selection of hematopoietic cells in vivo and for examining hematopoiesis-specific effects of mutations that are lethal during embryogenesis.
