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

Nature Medicine volume 6, pages 177–182 (2000)Cite this article

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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Figure 1: Globin chain analysis of AγSAD mice.
Figure 2: Immunofluorescence staining of AγSAD mice RBCs with antibody against γ globin chain.
Figure 3: Erythrocyte separation on a Stractan density discontinuous gradient.

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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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Authors and Affiliations

  1. Institut de Recherches Cliniques de Montreal, Molecular Genetics and Development, Faculte de Medecine de L'Universite de Montreal, Montreal, Quebec, Canada

    Marie-José Blouin, Hugues Beauchemin, Adrian Wright, Anne-Marie Bleau, Betty Nakamoto & Marie Trudel

  2. Dept of Pathology, Brown University School of Medicine, Providence, Rhode Island

    Monique De Paepe

  3. Bayer Corporation, Tarrytown, New York

    Martin Sorette

  4. Department of Medicine, University of Washington, Seattle, Washington

    Georges Stamatoyannopoulos

  5. Department of Pathology, Texas Children's Hospital Baylor College of Medicine, Houston, Texas

    Ching-Nan Ou

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  1. Marie-José Blouin
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  2. Hugues Beauchemin
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  9. Georges Stamatoyannopoulos
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Correspondence to Marie Trudel.

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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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