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Publication : Exogenous Mtv-7 superantigen transgene expression in major histocompatibility complex class II I-E- mice reconstituted with embryonic stem cell-derived hematopoietic stem cells.

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.
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