Establishment of an α-thalassemia mouse model through fetal liver cell transplantation and analysis of hematological parameters

Clinically, α-thalassemia is stratified into mild, intermediate, and severe forms, differentiated by the degree of anemia severity. Specifically, severe α-thalassemia manifests in homozygous individuals, characterized by a profound α globin deficit. The presence of two α0 alleles, resulting in a complete four-gene defect (α^--/--), constitutes a lethal in utero condition known as Hemoglobin (Hb) Barts hydrops fetalis syndrome. This arises from the inability of hemoglobin, deficient in α chains, to adequately transport oxygen. Consequently, this severe variant typically onsets during fetal development, often culminating in intrauterine death towards the end of gestation or dying shortly postpartum due to the compounded effects of severe anemia and resultant hypoxia. This study endeavors to establish an α-thalassemia mouse model via transplantation of embryonic liver cells harboring a dual α allele knockout, with a subsequent focus on comprehensively characterizing its hematological parameters and associated phenotypic indicators. To generate an α-globin chain-deficient mouse model, we transplanted fetal liver cells (harvested at embryonic day 13.5 from homozygous C57BL/6J-CD45.2-HBA-DKO mice) into C57BL/6 wild-type recipients preconditioned with 800 cGy irradiation. Multiple blood routine indicators, blood smear assessments, and spleen weight measurements, were subsequently conducted to characterize the model. Initially, model mice exhibited elevated white blood cell and lymphocyte counts relative to controls, potentially indicative of a possible immune reaction, though this response waned over time. Characteristic of the disease, these mice displayed significantly diminished mean corpuscular hemoglobin content and concentration, alongside heightened numbers of HbH inclusions and spleen weights. Furthermore, red blood cellindices, such as red blood cell count, hematocrit, red cell distribution width-coefficient of variation, and red cell distribution width-standard deviation, were all markedly increased in the model mice. Notably, model mice demonstrated significantly elevated values for mean platelet volume, platelet distribution width, and platelet large cell ratio percentage, reflective of aberrant platelet characteristics. Concurrently, a time-dependent increase in basophil percentages accompanied decreases in platelet count, platelet crit, and platelet larger cell count, collectively implying a progressively severe anemic state. Moreover, the progression from low to high levels of reticulocyte percentage and absolute reticulocyte count further corroborated an escalating tendency towards hemolysis. The model mice also experienced a substantial decline in body weight, underscoring the profound impact of disease progression on their health.