Transgenic mouse model of pharmacologic induction of fetal hemoglobin: Studies using a new ribonucleotide reductase inhibitor, didox

Evaluation of pharmacologic agents that stimulate fetal hemoglobin production has been done mainly in baboons and macaques. We investigated whether results in transgenic mice can predict the stimulation of fetal hemoglobin in primates, by testing γ globin induction in response to a new rlbonucleotide reductase inhibitor, Didox. A transgenic mouse line carrying the human Aγ gene linked to a locus control region cassette was used. Treatment of transgenic mice with Didox resulted in induction of γ gene expression as documented by an Increase in F reticulocytes and F cells and an elevation of γ/γ + β biosynthetic ratio. Similarly, administration of Didox to a baboon in the nonanemic and chronically anemic state resulted In induction of γ gene expression as shown by increases in F reticuiocytes, F cells, and Hb F. These results suggest that the μLR‐Aγ transgenic mice can be used to screen new pharmacologic compounds for γ globin inducibillty. © 1994 Wiley‐Liss, Inc.