Genetic correction of sickle cell disease: Insights using transgenic mouse models

• Published in: Nature medicine Vol. 6; no. 2; pp. 177 - 182
• Main Authors: Trudel, Marie, Blouin, Marie-José, Beauchemin, Hugues, Wright, Adrian, De Paepe, Monique, Sorette, Martin, Bleau, Anne-Marie, Nakamoto, Betty, Ou, Ching-Nan, Stamatoyannopoulos, Georges
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-02-2000
• Subjects: Anemia, Sickle Cell - genetics; Anemia, Sickle Cell - physiopathology; Anemia, Sickle Cell - therapy; Animals; Disease Models, Animal; Erythrocytes; Erythropoiesis - genetics; Fetal Hemoglobin - genetics; Genetic Therapy; Hematology; Hemoglobin; Life span; Longevity; Medicine; Mice; Mice, Transgenic; Pathology; Polymerization; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sickle cell disease; Transgenic animals; Canada; Montreal Quebec Canada
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/72279

Sickle cell disease is a hereditary disorder characterized by erythrocyte deformity due to hemoglobin polymerization. We assessed in vivo the potential curative threshold of fetal hemoglobin in the SAD transgenic mouse model of sickle cell disease using mating with mice expressing the human fetal Agamma-globin gene. With increasing levels of HbF, AgammaSAD mice showed considerable improvement in all hematologic parameters, morphopathologic features and life span/survival. We established the direct therapeutic effect of fetal hemoglobin on sickle cell disease and demonstrated correction by increasing fetal hemoglobin to about 9-16% in this mouse model. This in vivo study emphasizes the potential of the SAD mouse models for quantitative analysis of gene therapy approaches.