Abstract
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 Aγ-globin gene. With increasing levels of HbF, AγSAD 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.
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Acknowledgements
The authors thank M. Desforges for technical assistance. This work was supported by the Medical Research Council of Canada to M.T., the National Institutes of Health to G.S. and a Fonds pour la formation de chercheurs et d'aide a la recherche studentship to H.B.; M.T. is a chercheur-boursier of the Fonds de la Recherche en Santé due Québec.
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Blouin, MJ., Beauchemin, H., Wright, A. et al. Genetic correction of sickle cell disease: Insights using transgenic mouse models. Nat Med 6, 177–182 (2000). https://doi.org/10.1038/72279
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DOI: https://doi.org/10.1038/72279
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