Induction of HbF in SCD mice treated with RN-1. (A) Quantification of HbF by HPLC as a fraction of total hemoglobin in SCD mice either treated or untreated with RN-1 for 2 or 4 weeks (left panel); representative HPLC chromatograms depicting HbF abundance (shaded area) after 4 weeks RN-1 treatment (right panel). Other unmarked induced peaks may represent admixtures of murine embryonic εy and/or βh1 tetrameric hemoglobins (see below). (B) QRT-PCR quantification of γ-globin mRNA abundance as a fraction of the total of γ- plus β-globin mRNAs in SCD mice with or without RN-1 treatment of 2 and 4 weeks. (C-F) Fold change in the relative abundance of γ-globin mRNAs, normalized to the erythroid differentiation-invariant housekeeping mRNA, Oaz1, respectively.39 (G) QRT-PCR quantification of γ-, εy-, and βh1-globin mRNA abundance as a fraction of the total (γ-, εy- and βh1- plus β-globin mRNAs) in SCD mice with or without RN-1 treatment of 2 or 4 weeks. Statistically significant differences between RN-1–treated and untreated SCD mice are indicated (*P < .05; **P < .01). The bar graph data are presented as mean ± standard deviation (SD) (n = 4-6 mice per group).
