LINEAGE CONTROL OF AN INTEGRATION SITE-DE PENDENT TRANSGENE COMBINED WITH THE BETA-GLOBIN LOCUS-CONTROL REGION

In mice, the expression of integration site-dependent transgenes is co ntrolled by host DNA elements. These may involve locus control regions (LCR), enhancers and silencers. We analysed the interaction between t he LCR of the beta-globin locus (beta-LCR) and an integration site-dep endent LacZ transgene (HPRTnlsLacZ). We obtained LacZ expression in er ythroid cells of all transgenic mice, independent of temporal control, correlated to transgene copy-number. These results demonstrate that a n integration site-dependent transgene can be region-controlled by the beta-LCR and establish that the beta-LacZ transgenic lines constitute a valuable source of genetically marked cells for the three erythroid series. This also extends to in vivo regulation in all three erythroi d series the notion that the beta-LCR contains the information for reg ion-control of non-erythroid genes. In non-erythroid lineages of all m ice, we observed integration site-dependent LacZ expression. It sugges ts that a single LCR is not sufficient to insulate the LacZ gene from endogenous cis-acting control elements.