Research in the laboratory of Dr. Edward Rubin of the Life Sciences Division resulted in the creation of a new strain of mice that carries human hemoglobin genes with no counteracting mouse genes. This enables the mice to develop all clinical manifestations of sickle cell disease.

Each year approximately 100,000 babies in the world, mostly of African descent, are born with sickle cell disease, a painful and debilitating condition caused by a mutant hemoglobin gene. Although sickle cell disease has been extensively studied, there is still no effective treatment—a failure attributed in part to the lack of an animal model that accurately reproduces the disease's symptoms.

"This work marks the end of a long road to genetically engineer mice that faithfully model human sickle cell disease," says Rubin.

Transgenic mice containing the human sickle genes have been engineered before, but these mice developed only mild symptoms of the disease. The problem was that in addition to carrying the mutant human genes responsible for sickle cell disease, these strains also carried normal mouse genes which counteracted the defective human genes.

Through a series of complex transgenic and gene knock-out manipulations, the Berkeley Lab researchers were able to add the appropriate human genes as well as delete the (corresponding) mouse genes. The end products are mice with irreversibly sickled red blood cells, anemia, and multi-organ pathology.