Related Content
Search Google Scholar for:
|
|
Science 1 September 1989:
Vol. 245. no. 4921, pp. 971 - 973
DOI: 10.1126/science.2772649
|
|
Articles
Science, Vol 245, Issue 4921, 971-973
Copyright © 1989 by American Association for the Advancement of Science
Synthesis of functional human hemoglobin in transgenic mice
RR Behringer,
TM Ryan,
MP Reilly,
T Asakura,
RD Palmiter,
RL Brinster,
and
TM Townes
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Human alpha- and beta-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human beta-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human alpha- and beta-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Humanized Mouse Model of Cooley's Anemia.
- Y. Huo, S. C. McConnell, S.-R. Liu, R. Yang, T.-T. Zhang, C.-W. Sun, L.-C. Wu, and T. M. Ryan (2009)
J. Biol. Chem.
284, 4889-4896
| Abstract »
| Full Text »
| PDF »
- A Recombinant Human Hemoglobin with Anti-sickling Properties Greater than Fetal Hemoglobin.
- D. N. Levasseur, T. M. Ryan, M. P. Reilly, S. L. McCune, T. Asakura, and T. M. Townes (2004)
J. Biol. Chem.
279, 27518-27524
| Abstract »
| Full Text »
| PDF »
- Correction of a mouse model of sickle cell disease: lentiviral/antisickling {beta}-globin gene transduction of unmobilized, purified hematopoietic stem cells.
- D. N. Levasseur, T. M. Ryan, K. M. Pawlik, and T. M. Townes (2003)
Blood
102, 4312-4319
| Abstract »
| Full Text »
| PDF »
- Retrograde trans-synaptic transfer of green fluorescent protein allows the genetic mapping of neuronal circuits in transgenic mice.
- U. Maskos, K. Kissa, C. St. Cloment, and P. Brulet (2002)
PNAS
99, 10120-10125
| Abstract »
| Full Text »
| PDF »
- In vivo transfer of GPI-linked complement restriction factors from erythrocytes to the endothelium.
- D. Kooyman, G. Byrne, S McClellan, D Nielsen, M Tone, H Waldmann, T. Coffman, K. McCurry, J. Platt, and J. Logan (1995)
Science
269, 89-92
| Abstract »
| PDF »
- A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus..
- W C Forrester, E Epner, M C Driscoll, T Enver, M Brice, T Papayannopoulou, and M Groudine (1990)
Genes & Dev.
4, 1637-1649
| Abstract »
| PDF »
- A major positive regulatory region located far upstream of the human alpha-globin gene locus..
- D R Higgs, W G Wood, A P Jarman, J Sharpe, J Lida, I M Pretorius, and H Ayyub (1990)
Genes & Dev.
4, 1588-1601
| Abstract »
| PDF »
- beta-globin dominant control region interacts differently with distal and proximal promoter elements..
- M Antoniou and F Grosveld (1990)
Genes & Dev.
4, 1007-1013
| Abstract »
| PDF »
- Human gamma- to beta-globin gene switching in transgenic mice..
- R R Behringer, T M Ryan, R D Palmiter, R L Brinster, and T M Townes (1990)
Genes & Dev.
4, 380-389
| Abstract »
| PDF »
- Human sickle hemoglobin in transgenic mice.
- T. Ryan, T. Townes, M. Reilly, T Asakura, R. Palmiter, R. Brinster, and R. Behringer (1990)
Science
247, 566-568
| Abstract »
| PDF »
|
|
