Establishment and characterization of the male erythroid phenotypes of XLSA and XLPP mouse models. (A) Schematic of key erythroid heme biosynthetic substrates and intermediates (left); mouse models used in this study (right). (B) Targeted mutations in the human ALAS2 genomic locus. XLSA mutations are indicated in blue, and XLPP mutations are in red. (C) Chromatograms of targeted mutations, including the protospacer-associated motif (PAM) site silent mutation (in black) that were created in addition to the coding sequence variants introduced (in blue or red). (D) Selected RBC indices for male mice of XLSA, XLPP, and EPP models maintained on conventional rodent chow at ages 5, 8, 24, and 54 weeks. (E) Spleen-to-body mass ratio at ages 8 and 54 weeks. (F) Serum erythropoietin (EPO) at ages 8 and 54 weeks. The dotted line in each panel indicates the average value in control animals. n = 3 to 6 mutants per group; n = 13 to 23 controls. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001, compared with control animals at the same age. B6, pyridoxine; B-thal, beta-thalassemia; CTL, control; CHr, hemoglobin of the reticulocyte; HBA/HBB, hemoglobin α/β; MCV, mean corpuscular volume.