| First Author | Chambers CA | Year | 1994 |
| Journal | Proc Natl Acad Sci U S A | Volume | 91 |
| Issue | 3 | Pages | 1138-42 |
| PubMed ID | 8302843 | Mgi Jnum | J:16712 |
| Mgi Id | MGI:64776 | Doi | 10.1073/pnas.91.3.1138 |
| Citation | Chambers CA, et al. (1994) Exogenous Mtv-7 superantigen transgene expression in major histocompatibility complex class II I-E- mice reconstituted with embryonic stem cell-derived hematopoietic stem cells. Proc Natl Acad Sci U S A 91(3):1138-42 |
| abstractText | 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. |