Nucleic Acids Research, 1992, Vol. 20, No. 7 1503-1509
© 1992
MOLECULAR BIOLOGY |
Functional analysis of defined mutations in the immunoglobulin heavy-chain enhancer in transgenic mice
Zentrum für Molekulare Biologie Heidelberg Im Neuenheimer Feld 282, D-6900 Heidelberg, Germany 1Basel Institute for Immunology Grenzacherstrasse 487, CH-4005 Basel, Switzerland
Received January 30, 1992. Revised March 11, 1992. Accepted March 11, 1992.
We have analyzed the effect of defined mutations In the mouse immunoglobulin heavy-chain enhancer after introduction into the germline of transgenic mice. We have tested a mutation of the enhancer octamer motif, a double mutation of the octamer motif and the µB-site, and a triple mutation in the µE2, µE3 and µE4-sites. All constructs are expressed in the spleen of transgenic mice. Furthermore, expression is exclusively detectable in lymphoid organs and not in several non-lymphoid tissues. Whereas mutations in the µE-sites have a more pronounced effect on transgene activity in thymocytes as compared to bone marrow and spleen cells, the octamer/µB double mutation shows significantly reduced expression levels only in B-cells. Finally, our results demonstrate that the intronic heavy-chain enhancer element does not contribute to the increase in steady state levels of heavy-chain mRNA after stimulation of spleen cells with LPS.
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