Hb switching and survival curves of humanized γ^HPFH δβ⁰ CA mice. (A) Humanized compound heterozygous γ^HPFHδβ⁰/γβ^A mice complete the switch from high levels of fetal γ globin to adult δ and β globins after birth. Weekly hemolysates from peripheral blood were analyzed by HPLC to quantify the β-like globin chains. The fractional percentage of γ (□), β (◇), and δ (▵) globin chains relative to total β-like chains is plotted over time. Values represent mean ± SEM, n = 8. (B) Survival curves of humanized homozygous γ^HPFHδβ⁰ CA (□) and littermate control (◇) mice. The majority of fully humanized γ^HPFHδβ⁰ CA mice expire within 3 weeks of age as the human γ globin switches to the human δ and nonfunctional human β⁰ globin genes. Moribund homozygous CA mice were humanely euthanized before death, and their genotype was confirmed by PCR of tail tip DNA. All humanized littermate control mice (γ^HPFHδβ⁰/γβ^A and γβ^A/γβ^A) survived beyond 5 weeks of age.