TRANSGENIC ANIMAL-MODELS OF SICKLE-CELL DISEASE

An animal model which allows study of chronic processes occurring in sickle cell disease has finally been realized with the development of several lines of transgenic mice which express high levels of beta(s) or beta(s)-variants in their red cells. The red cells of all mouse lines exhibit characteristic sickle shapes on deoxygenation and most lines have enlarged spleens and mildly elevated reticulocytes in adult mice; both of these properties are suggestive of enhanced red cell destruction and erythropoiesis. However, all lines examined to date have normal hemoglobin levels in adult mice. In one mouse line under ambient conditions, retinopathy and abnormal renal function have been observed and in the same line under hypoxic conditions, anemia, irreversibly sickled cell formation, and urine concentrating defect have been observed. The current mouse lines will allow some aspects of sickle cell disease to be studied, but significant improvements can still be made in the transgenic mouse model.