FUNCTIONAL-ANALYSIS OF DEFINED MUTATIONS IN THE IMMUNOGLOBULIN HEAVY-CHAIN ENHANCER IN TRANSGENIC MICE

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 mu-B-site, and a triple mutation in the mu-E2, mu-E3 and mu-E4-sites. All constructs are expressed in the spleen of transgenic mice. Furthermore, expression is exclusively detectable in lymphoid organs and not in several nonlymphoid tissues. Whereas mutations in the mu-E-sites have a more pronounced effect on transgene activity in thymocytes as compared to bone marrow and spleen cells, the octamer/mu-B 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.