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. 1994 Feb 1;91(3):1138–1142. doi: 10.1073/pnas.91.3.1138

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

C A Chambers 1, J Kang 1, J Pawling 1, B Huber 1, N Hozumi 1, A Nagy 1
PMCID: PMC521469  PMID: 8302843

Abstract

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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Selected References

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