Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 31 October 1997:
Vol. 278. no. 5339, pp. 873 - 876
DOI: 10.1126/science.278.5339.873
Prev | Table of Contents | Next

Reports

Knockout-Transgenic Mouse Model of Sickle Cell Disease

T. M. Ryan, D. J. Ciavatta, T. M. Townes *

When transgenic mice that expressed human sickle hemoglobin were mated with mice having knockout mutations of the mouse alpha - and beta -globin genes, animals were produced that synthesized only human hemoglobin in adult red blood cells. Similar to many human patients with sickle cell disease, the mice developed a severe hemolytic anemia and extensive organ pathology. Numerous sickled erythrocytes were observed in peripheral blood. Although chronically anemic, most animals survived for 2 to 9 months and were fertile. Drug and genetic therapies can now be tested in this mouse model of sickle cell disease.

Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
*   To whom correspondence should be addressed. E-mail: ttownes{at}bmg.bhs.uab.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Preclinical transfusion-dependent humanized mouse model of {beta} thalassemia major.
Y. Huo, S. C. McConnell, and T. M. Ryan (2009)
Blood 113, 4763-4770
   Abstract »    Full Text »    PDF »
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 »
Arginine therapy of transgenic-knockout sickle mice improves microvascular function by reducing non-nitric oxide vasodilators, hemolysis, and oxidative stress.
D. K. Kaul, X. Zhang, T. Dasgupta, and M. E. Fabry (2008)
Am J Physiol Heart Circ Physiol 295, H39-H47
   Abstract »    Full Text »    PDF »
Gene Replacement Therapy for Sickle Cell Disease and Other Blood Disorders.
T. M. Townes (2008)
Hematology 2008, 193-196
   Abstract »    Full Text »    PDF »
Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin.
J. Hanna, M. Wernig, S. Markoulaki, C.-W. Sun, A. Meissner, J. P. Cassady, C. Beard, T. Brambrink, L.-C. Wu, T. M. Townes, et al. (2007)
Science 318, 1920-1923
   Abstract »    Full Text »    PDF »
Report on the Workshop "New Technologies in Stem Cell Research," Society for Pediatric Research, San Francisco, California, April 29, 2006.
J. C. Cheng, K. M. Sakamoto, E. M. Horwitz, S. L. Karsten, L. Shoemaker, H. I. Kornblumc, and P. Malik (2007)
Stem Cells 25, 1070-1088
   Abstract »    Full Text »    PDF »
Correction of sickle cell disease by homologous recombination in embryonic stem cells.
L.-C. Wu, C.-W. Sun, T. M. Ryan, K. M. Pawlik, J. Ren, and T. M. Townes (2006)
Blood 108, 1183-1188
   Abstract »    Full Text »    PDF »
Humanized beta-Thalassemia Mouse Model Containing the Common IVSI-110 Splicing Mutation.
J. Vadolas, M. Nefedov, H. Wardan, S. Mansooriderakshan, L. Voullaire, D. Jamsai, R. Williamson, and P. A. Ioannou (2006)
J. Biol. Chem. 281, 7399-7405
   Abstract »    Full Text »    PDF »
Correction of the sickle cell mutation in embryonic stem cells.
J. C. Chang, L. Ye, and Y. W. Kan (2006)
PNAS 103, 1036-1040
   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 »
Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells.
J. R. Romero, S. M. Suzuka, R. L. Nagel, and M. E. Fabry (2004)
Blood 103, 2384-2390
   Abstract »    Full Text »    PDF »
Increased erythrocyte adhesion in mice and humans with hereditary spherocytosis and hereditary elliptocytosis.
N. J. Wandersee, S. C. Olson, S. L. Holzhauer, R. G. Hoffmann, J. E. Barker, and C. A. Hillery (2004)
Blood 103, 710-716
   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 »
ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice.
J. W. Stocker, L. De Franceschi, G. A. McNaughton-Smith, R. Corrocher, Y. Beuzard, and C. Brugnara (2003)
Blood 101, 2412-2418
   Abstract »    Full Text »    PDF »
Nitric Oxide-dependent Generation of Reactive Species in Sickle Cell Disease. ACTIN TYROSINE NITRATION INDUCES DEFECTIVE CYTOSKELETAL POLYMERIZATION.
M. Aslan, T. M. Ryan, T. M. Townes, L. Coward, M. C. Kirk, S. Barnes, C. B. Alexander, S. S. Rosenfeld, and B. A. Freeman (2003)
J. Biol. Chem. 278, 4194-4204
   Abstract »    Full Text »    PDF »
Hemoglobinopathies.
G. F. Atweh, J. DeSimone, Y. Saunthararajah, H. Fathallah, R. S. Weinberg, R. L. Nagel, M. E. Fabry, and R. J. Adams (2003)
Hematology 2003, 14-39
   Abstract »    Full Text »    PDF »
A human embryonic hemoglobin inhibits Hb S polymerization in vitro and restores a normal phenotype to mouse models of sickle cell disease.
Z. He and J. E. Russell (2002)
PNAS 99, 10635-10640
   Abstract »    Full Text »    PDF »
Mouse surviving solely on human erythropoietin receptor (EpoR): model of human EpoR-linked disease.
V. Divoky, J. T. Prchal ;, X. Yu, and C. T. Noguchi (2002)
Blood 99, 3873-3875
   Full Text »    PDF »
Primary role for adherent leukocytes in sickle cell vascular occlusion: A new paradigm.
A. Turhan, L. A. Weiss, N. Mohandas, B. S. Coller, and P. S. Frenette (2002)
PNAS 99, 3047-3051
   Abstract »    Full Text »    PDF »
A cure for murine sickle cell disease through stable mixed chimerism and tolerance induction after nonmyeloablative conditioning and major histocompatibility complex-mismatched bone marrow transplantation.
L. S. Kean, M. M. Durham, A. B. Adams, L. L. Hsu, J. R. Perry, D. Dillehay, T. C. Pearson, E. K. Waller, C. P. Larsen, and D. R. Archer (2002)
Blood 99, 1840-1849
   Abstract »    Full Text »    PDF »
Renal Pathology in Hemizygous Sickle Cell Mice.
B.A. Diwan, M.T. Gladwin, C.T. Noguchi, J.M. Ward, A.L. Fitzhugh, and G.S. Buzard (2002)
Toxicol Pathol 30, 254-262
   Abstract »    PDF »
Targeted disruption of the activating transcription factor 4 gene results in severe fetal anemia in mice.
H. C. Masuoka and T. M. Townes (2002)
Blood 99, 736-745
   Abstract »    Full Text »    PDF »
Reaping of nitric oxide by sickle cell disease.
J. R. Lancaster Jr. (2002)
PNAS 99, 552-553
   Full Text »    PDF »
The hypercoagulable state in thalassemia.
A. Eldor and E. A. Rachmilewitz (2002)
Blood 99, 36-43
   Abstract »    Full Text »    PDF »
Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease.
M. Aslan, T. M. Ryan, B. Adler, T. M. Townes, D. A. Parks, J. A. Thompson, A. Tousson, M. T. Gladwin, R. P. Patel, M. M. Tarpey, et al. (2001)
PNAS 98, 15215-15220
   Abstract »    Full Text »    PDF »
Correction of Sickle Cell Disease in Transgenic Mouse Models by Gene Therapy.
R. Pawliuk, K. A. Westerman, M. E. Fabry, E. Payen, R. Tighe, E. E. Bouhassira, S. A. Acharya, J. Ellis, I. M. London, C. J. Eaves, et al. (2001)
Science 294, 2368-2371
   Abstract »    Full Text »    PDF »
Lack of neighborhood effects from a transcriptionally active phosphoglycerate kinase-neo cassette located between the murine {beta}-major and {beta}-minor globin genes.
R. M. Kaufman, Z. H. Lu, R. Behl, J. M. Holt, G. K. Ackers, and T. J. Ley (2001)
Blood 98, 65-73
   Abstract »    Full Text »    PDF »
Expression, purification, and characterization of human hemoglobins Gower-1 ({zeta}2{epsilon}2), Gower-2 ({alpha}2{epsilon}2), and Portland-2 ({zeta}2{beta}2) assembled in complex transgenic-knockout mice.
Z. He and J. E. Russell (2001)
Blood 97, 1099-1105
   Abstract »    Full Text »    PDF »
Second generation knockout sickle mice: the effect of HbF.
M. E. Fabry, S. M. Suzuka, R. S. Weinberg, C. Lawrence, S. M. Factor, J. G. Gilman, F. Costantini, and R. L. Nagel (2001)
Blood 97, 410-418
   Abstract »    Full Text »    PDF »
Mechanisms of vascular instability in a transgenic mouse model of sickle cell disease.
K. A. Nath, V. Shah, J. J. Haggard, A. J. Croatt, L. A. Smith, R. P. Hebbel, and Z. S. Katusic (2000)
Am J Physiol Regulatory Integrative Comp Physiol 279, R1949-R1955
   Abstract »    Full Text »    PDF »
Induction of Human Fetal Globin Gene Expression by a Novel Erythroid Factor, NF-E4.
W. Zhou, D. R. Clouston, X. Wang, L. Cerruti, J. M. Cunningham, and S. M. Jane (2000)
Mol. Cell. Biol. 20, 7662-7672
   Abstract »    Full Text »
Lentiviral Vector Transduction of Hematopoietic Stem Cells that Mediate Long-Term Reconstitution of Lethally Irradiated Mice.
W. Chen, X. Wu, D. N. Levasseur, H. Liu, L. Lai, J. C. Kappes, and T. M. Townes (2000)
Stem Cells 18, 352-359
   Abstract »    Full Text »
Human {gamma}-globin gene promoter element regulates human {beta}-globin gene developmental specificity.
T. M. Ryan, C.-W. Sun, J. Ren, and T. M. Townes (2000)
Nucleic Acids Res. 28, 2736-2740
   Abstract »    Full Text »    PDF »
Gene therapy for the hemoglobin disorders: Past, present, and future.
D. A. Persons and A. W. Nienhuis (2000)
PNAS 97, 5022-5024
   Full Text »    PDF »
Formation of Dense Erythrocytes in SAD Mice Exposed to Chronic Hypoxia: Evaluation of Different Therapeutic Regimens and of a Combination of Oral Clotrimazole and Magnesium Therapies.
L. De Franceschi, C. Brugnara, P. Rouyer-Fessard, H. Jouault, and Y. Beuzard (1999)
Blood 94, 4307-4313
   Abstract »    Full Text »    PDF »
Altered Hematopoiesis in Murine Sickle Cell Disease.
M.-J. Blouin, M. E. De Paepe, and M. Trudel (1999)
Blood 94, 1451-1459
   Abstract »    Full Text »    PDF »
Transgenic knockout mice exclusively expressing human hemoglobin S after transfer of a 240-kb beta s-globin yeast artificial chromosome: A mouse model of sickle cell anemia.
J. C. Chang, R. Lu, C. Lin, S.-M. Xu, Y. W. Kan, S. Porcu, E. Carlson, M. Kitamura, S. Yang, L. Flebbe-Rehwaldt, et al. (1998)
PNAS 95, 14886-14890
   Abstract »    Full Text »    PDF »
Substitution of the Human beta -Spectrin Promoter for the Human Agamma -Globin Promoter Prevents Silencing of a Linked Human beta -Globin Gene in Transgenic Mice.
D. E. Sabatino, A. P. Cline, P. G. Gallagher, L. J. Garrett, G. Stamatoyannopoulos, B. G. Forget, and D. M. Bodine (1998)
Mol. Cell. Biol. 18, 6634-6640
   Abstract »    Full Text »
A Knockout of a Transgenic Mouse -- Animal Models of Sickle Cell Anemia.
R. L. Nagel (1998)
N. Engl. J. Med. 339, 194-195
   Full Text »
MOUSE MODEL FOR SICKLE CELL ANEMIA.
(1997)
Journal Watch (General) 1997, 5
   Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)