Investigations of the induction of the goat βC globin gene by erythropoietin: Studies in transgenic mice

The genes of the beta globin locus of sheep and goats undergo three developmental switches, from embryonic ε to fetal γ to juvenile βC and from βC to adult βA. The juvenile βC gene of adult goats and sheep are strikingly induced by erythropoietin (Epo). To obtain insights on the mechanism of βC induction by Epo, we produced transgenic mice carrying various βC gene constructs and examined the inducibility of the βC gene following administration of high doses of erythropoietin. None of the treatments resulted in reproducible induction of the βC gene by erythropoietin. We conclude that the Epo inducibility elements are not contained in the 4.7 kb (which included 0.88 kb of the βC promoter and 2.3 kb downstream sequence) βC gene we used or that a trans-acting environment specific to the goat and sheep erythroid cell lineage is required for induction of the βC globin gene by erythropoietin.