Format

Send to

Choose Destination
J Clin Invest. 1991 Feb;87(2):639-47.

Hypoxia-induced in vivo sickling of transgenic mouse red cells.

Author information

1
Division of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.

Abstract

To develop an animal model for sickle cell anemia, we have created transgenic mice that express a severe naturally occurring human sickling hemoglobin, Hb S Antilles. Due to its low solubility and oxygen affinity, Hb S Antilles has a greater propensity to cause red cell sickling than Hb S. To make transgenic animals that express a high level of Hb S Antilles, the erythroid-specific DNAse I hypersensitive site II from the human beta-globin cluster was linked independently to the human alpha 2-globin gene and to the beta S Antilles gene. Embryos were injected with both constructs simultaneously and seven transgenic mice were obtained, three of which contained both the human alpha and the human beta S Antilles transgene. After crossing the human transgenes into the mouse beta-thalassemic background a transgenic mouse line was derived in which approximately half the beta-globin chains in the murine red cells were human beta S Antilles. Deoxygenation of the transgenic red cells in vitro resulted in extensive sickling. An increase of in vivo sickling was achieved by placing these transgenic mice in a low oxygen environment. This murine model for red cell sickling should help to advance our understanding of sickle cell disease and may provide a model to test therapeutic interventions.

PMID:
1991848
PMCID:
PMC296354
DOI:
10.1172/JCI115041
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center