Hypoxia-induced in vivo sickling of transgenic mouse ...
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Citation
| Title | Hypoxia-induced in vivo sickling of transgenic mouse red cells |
| Author(s) | E. Rubin, H. Witkowska, E. Spangler, P. Curtin, B. Lubin, N. Mohandas, S. Clift |
| Journal | The Journal of clinical investigation |
| Date | 1991 |
| Volume | 87 |
| Issue | 2 |
| Start page | 639 |
| End page | 647 |
| 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. |
| ISSN | 0021-9738 |
| Use/Reproduction | Contact Publisher |
| Text | http://www.islandscholar.ca/download_ds/ir:ir-batch6-2588/PDF |
Using APA 6th Edition citation style.
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