COMPARISON OF EXPRESSION OF HUMAN GLOBIN GENES TRANSFERRED INTO MOUSEERYTHROLEUKEMIA-CELLS AND IN TRANSGENIC MICE

To examine whether transfer of gamma globin genes into mouse erythrole ukemia cells can be used for the analysis of regulatory elements of ga mma globin gene promoter, (A)gamma gene constructs carrying promoter t runcations that have been previously analyzed in transgenic mice were used for production of stably transfected mouse erythroleukemia (MEL) cell clones and pools. We found that constructs, which contain a micro locus control region (mu LCR) that efficiently protects globin gene ex pression from the effects of the position of integration in transgenic mice, display position-dependent globin gene expression in MEL cell c lones. (A)gamma globin gene expression among MEL cell clones carrying the mu LCR(-201)(A)gamma and mu LCR(-382)(A)gamma gene constructs rang ed 15.5-fold and 17.6-fold, respectively, and there was no correlation between the (A)gamma mRNA levels and the copies of the transgene (r = .28, P =.18). There was significant variation in per copy (A)gamma glo bin gene expression among MEL cell pools composed of 10 clones, but no t among pools composed of 50 clones, indicating that position effects are averaged in pools composed by large numbers of clones. The overall pattern of (A)gamma globin gene expression in MEL cell pools resemble d that observed in transgenic mice indicating that MEL cell transfecti ons can be used in the study of cis elements controlling gamma globin gene expression. MEL cell transfections, however, are not appropriate for investigation of cis elements, which either sensitize or protect t he globin transgenes from position effects. (C) 1998 by The American S ociety of Hematology.