A transgenic mouse model of sickle cell disorder (original) (raw)

Nature volume 343, pages 183–185 (1990) Cite this article

Abstract

A SINGLE base-pair mutation (βs) in codon 6 of the human β-globin gene, causing a single amino-acid substitution, is the cause of sickle cell anaemia1. The mutant haemoglobin molecule, HbS, polymerizes when deoxygenated and causes deformation of the erythrocytes to a characteristic 'sickled' shape. Sickling of cells in small vessels causes painful crises and other life-threatening complications2,3. Although the molecular basis for sickle cell anaemia has been known for 30 years, no definitive treatment is available4. An animal model of sickle cell anaemia would not only allow a detailed analysis of the factors that initiate erythrocyte sickling in vivo and of the pathophysiology of the disease, but would also permit the development of novel approaches to the treatment of the disease. By using the dominant control region sequences from the human β-globin locus, together with human α and βS-globin genes, we have obtained three transgenic mice with HbS levels ranging from 10 to 80% of total haemoglobin in their red cells. As observed in homozygous and heterozygous Hbspatients, the erythrocytes of this mouse sickle readily on deoxygenation. Irreversibly sickled cells2,3, which are characteristic of sickle-cell patients homozygous for βs, are also observed in the peripheral blood of the mouse with high levels of HbS.

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Author notes

  1. Michael J. Hedges, David Ropers and Lucio Luzzatto: Haematology Department, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK

Authors and Affiliations

  1. Laboratory of Gene Structure and Expression, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
    David R. Greaves, Peter Fraser, Miguel A. Vidal, Michael J. Hedges, David Ropers, Lucio Luzzatto & Frank Grosveld

Authors

  1. David R. Greaves
  2. Peter Fraser
  3. Miguel A. Vidal
  4. Michael J. Hedges
  5. David Ropers
  6. Lucio Luzzatto
  7. Frank Grosveld

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Greaves, D., Fraser, P., Vidal, M. et al. A transgenic mouse model of sickle cell disorder.Nature 343, 183–185 (1990). https://doi.org/10.1038/343183a0

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