Modèles expérimentaux de β-Thalassémie

Abstract

Experimental models for human genetic diseases prove to be helpful to improve our understanding of pathophysiological mechanisms and to devise new therapeutic approaches. An in vitro model consisted in entrapping purified alpha hemoglobin chains within normal erythrocytes by reversible osmotic lysis. This in vitro model for the beta thalassemic erythrocyte provided a tool by which the fate of excess alpha chains, and their cellular pathophysiological effects could be examined. Moreover, this model can be used to evaluate new therapeutic approaches, before their use in the animal model. Because of the differences between man and mice, a mouse model seldom reproduces faithfully a human disease. Nevertheless, pathophysiological features may be common to mice and men, giving thereby new insights in the human disease. Although molecular defects giving rise to murine beta thalassemia are quite different from those reported in the human disease, both diseases lead to similar cellular abnormalities of red blood cells. The study of the mouse model of beta thalassemia allowed us to progress in the understanding of the cellular defects leading to anemia, and to evaluate in vivo new agents improving the globin chain synthesis. New therapeutic approaches compensate the defect of the beta gene by increasing the expression of homologous genes, fetal in human or beta minor in mice. Hydroxyurea and recombinant erythropoietin decrease the severity of the mouse disease.