TY - JOUR
T1 - Expression of human IFN-γ genomic DNA in transgenic mice
AU - Young, H. A.
AU - Komschlies, K. L.
AU - Ciccarone, V.
AU - Beckwith, M.
AU - Rosenberg, M.
AU - Jenkins, N. A.
AU - Copeland, N. G.
AU - Durum, S. K.
PY - 1989
Y1 - 1989
N2 - We have introduced an 8.6-kb fragment of human genomic DNA containing the full length IFN-γ gene into the mouse germline. The transgenic animals had no biologic or developmental defects as human IFN-γ does not bind to the mouse IFN R. Regulation of the transgene paralleled that of the endogenous murine IFN-γ gene in that: 1) it is not expressed constitutively in any tissue examined thus far, 2) it can be induced in thymus and spleen cell by T cell mitogens, 3) it is not expressed in B cells stimulated by LPS, and 4) it produces normal mRNA and biologically active IFN protein. Whereas expression of the transgene is likely restricted to T cells, we had observed that both fibroblasts and B cell lines could express the same DNA when transfected in vitro; this indicates that in vivo, developmental factors restrict expression of the IFN-γ gene to T cells. These findings also indicate that the 8.6-kb fragment contains the regulatory elements necessary for normal tissue specific expression in vivo. Moreover, they indicate that the regulatory elements for this gene are completely preserved over the phylogenetic distance separating mouse and man, even though substantial drift has occurred in the structural gene, and probably in the IFN-γ R as well.
AB - We have introduced an 8.6-kb fragment of human genomic DNA containing the full length IFN-γ gene into the mouse germline. The transgenic animals had no biologic or developmental defects as human IFN-γ does not bind to the mouse IFN R. Regulation of the transgene paralleled that of the endogenous murine IFN-γ gene in that: 1) it is not expressed constitutively in any tissue examined thus far, 2) it can be induced in thymus and spleen cell by T cell mitogens, 3) it is not expressed in B cells stimulated by LPS, and 4) it produces normal mRNA and biologically active IFN protein. Whereas expression of the transgene is likely restricted to T cells, we had observed that both fibroblasts and B cell lines could express the same DNA when transfected in vitro; this indicates that in vivo, developmental factors restrict expression of the IFN-γ gene to T cells. These findings also indicate that the 8.6-kb fragment contains the regulatory elements necessary for normal tissue specific expression in vivo. Moreover, they indicate that the regulatory elements for this gene are completely preserved over the phylogenetic distance separating mouse and man, even though substantial drift has occurred in the structural gene, and probably in the IFN-γ R as well.
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M3 - Article
C2 - 2506285
AN - SCOPUS:0024330419
VL - 143
SP - 2389
EP - 2394
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -