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Effects of alpha thalassemia on mouse development.

Matings were made between (1) normal mice, (2) heterozygous alpha thalassemic females and normal males, and (3) heterozygous alpha thalassemic mice to produce litters of (1) normal mice, (2) normal and heterozygous alpha thalassemic mice, and (3) normal, heterozygous, and homozygous alpha thalassemic mice, respectively, in order to determine what effects the heterozygous and homozygous forms of alpha thalassemia might have on mouse development. Genetic tests showed that the viable alpha thalassemic progeny of matings between heterozygous alpha thalassemic mice were heterozygotes which suggests that the homozygotes die. Examination of preimplantation embryos from the uterus of normal and heterozygous alpha thalassemic females at 86 h after mating with normal males showed that these embryos had reached the blastocyst stage of development. When heterozygous alpha thalassemic females were mated with heterozygous alpha thalassemic males, however, only three-fourths of the embryos had reached the early blastocyst stage of development at 86 h, while one-fourth of them (presumed homozygous alpha thalassemic embryos) were still at the morula stage of development. At 11.5 though 15.5 days of gestation, about one-fourth of the implantation sites did not contain live fetuses, which suggests that death had occurred earlier. Histologic examination of embryos at 5.5 though 8.5 days of gestation showed that the homozygous alpha thalassemic embryos implanted and developed to the late blastocyst stage, at which time they became necrotic. Microscopic examination of blood films from fetuses at 11.5 through 15.5 days of development showed that the yolk sac-derived erythrocytes of alpha thalassemic heterozygotes were morphologically normal, but the fetal liver-derived erythrocytes contained eosinophilic inclusions. Electrophoresis of blood from the fetuses showed that alpha thalassemic heterozygotes contained a unique embryonic hemoglobin (y4), which is homologous to Bart's γ4 in humans.