scholarly journals A transgenic mouse model of sickle cell disorder

Nature ◽  
1990 ◽  
Vol 343 (6254) ◽  
pp. 183-185 ◽  
Author(s):  
David R. Greaves ◽  
Peter Fraser ◽  
Miguel A. Vidal ◽  
Michael J. Hedges ◽  
David Ropers ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Transgenic Mouse Model ◽  
Cell Disorder

Mechanisms of vascular instability in a transgenic mouse model of sickle cell disease

2000 ◽  
Vol 279 (6) ◽  
pp. R1949-R1955 ◽  
Author(s):  
K. A. Nath ◽  
V. Shah ◽  
J. J. Haggard ◽  
A. J. Croatt ◽  
L. A. Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Lipid Peroxidation ◽  
Sickle Cell Disease ◽  
Mouse Model ◽  
Systolic Blood Pressure ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Transgenic Mouse Model ◽  
Cell Disease

We investigated a transgenic mouse model of sickle cell disease, homozygous for deletion of mouse β-globin and containing transgenes for human βSand βS-antillesglobins linked to the transgene for human α-globin. In these mice, basal cGMP production in aortic rings is increased, whereas relaxation to an endothelium-dependent vasodilator, A-23187, is impaired. In contrast, aortic expression of endothelial nitric oxide synthase (NOS) is unaltered in sickle mice, whereas expression of inducible NOS is not detected in either group; plasma nitrate/nitrite concentrations and NOS activity are similar in both groups. Increased cGMP may reflect the stimulatory effect of peroxides (an activator of guanylate cyclase), because lipid peroxidation is increased in aortae and in plasma in sickle mice. Despite increased vascular cGMP levels in sickle mice, conscious systolic blood pressure is comparable to that of aged-matched controls; sickle mice, however, evince a greater rise in systolic blood pressure in response to nitro-l-arginine methyl ester, an inhibitor of NOS. Systemic concentrations of the vasoconstrictive oxidative product 8-isoprostane are increased in sickle mice. We conclude that vascular responses are altered in this transgenic sickle mouse and are accompanied by increased lipid peroxidation and production of cGMP; we suggest that oxidant-inducible vasoconstrictor systems such as isoprostanes may oppose nitric oxide-dependent and nitric oxide-independent mechanisms of vasodilatation in this transgenic sickle mouse. Destabilization of the vasoactive balance in the sickle vasculature by clinically relevant states may predispose to vasoocclusive disease.

scholarly journals Systematic Enhancement of Polymerization of Recombinant Sickle Hemoglobin Mutants: Implications for Transgenic Mouse Model for Sickle Cell Anemia

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4620-4627 ◽  
Author(s):  
Xianfeng Li ◽  
Urooj A. Mirza ◽  
Brian T. Chait ◽  
James M. Manning
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
High Performance ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Quantitative Information ◽  
Transgenic Mouse Model ◽  
Sickle Hemoglobin

Abstract To provide quantitative information on the sites that promote polymerization of sickle hemoglobin (HbS) after formation of the initial hydrophobic bond involving Val-6(β) [E6V(β)] and also to provide hemoglobins with an enhanced polymerization that could be used in a mouse model for sickle cell anemia, we have expressed recombinant double, triple, and quadruple HbS mutants with substitutions on both the α- and β-chains, E6V(β)/E121R(β), D75Y(α)/E6V(β)/E121R(β) and D6A(α)/D75Y(α)/E6V(β)/E121R(β). These recombinant hemoglobins were extensively characterized by high-performance liquid chromatography analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, amino acid analysis, and mass spectroscopy. They retained the functional properties of the Hb tetramer and polymerized in a linear manner at progressively lower Hb concentration as a function of the degree of substitution, suggesting that these remote sites (αD6A, αD75Y, and βE121R) on the α- and β-chains exhibit additive, enhanced polymerization properties. The quadruple mutant has a polymerization concentration close to that of the purified SAD hemoglobin from transgenic mouse red blood cells consisting of HbS, Hb Antilles, and Hb D-Punjab. Normal mouse Hb increases the polymerization concentration of each mutant. Thus, the general approach of using recombinant Hbs as described here should prove useful in elucidating the quantitative aspects of the mechanism of HbS polymerization and in identifying the contribution of individual sites to the overall process. The strategy described here demonstrates the feasibility of a systematic approach to achieve future recombinant HbS mutants that could provide a new generation of the transgenic mouse model for sickle cell anemia.

scholarly journals A Transgenic Mouse Model for Human Sickle Cell Disease

1990 ◽  
Vol 6 ◽  
pp. 6-12
Author(s):  
Richard R. BEHRINGER ◽  
Thomas M. RYAN ◽  
Michael P. REILLY ◽  
Toshio ASAKURA ◽  
Richard D. PALMITER ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Transgenic Mouse Model ◽  
Cell Disease

scholarly journals Activation of blood platelets in a transgenic mouse model of sickle cell disease

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Renata K Polanowska‐Grabowska ◽  
Robert A. Figler ◽  
Melissa M Marshall ◽  
Kori Wallace ◽  
Adrian R. L. Gear ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Blood Platelets ◽  
Transgenic Mouse Model ◽  
Cell Disease

scholarly journals Dietary  -3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease

Haematologica ◽  
2015 ◽  
Vol 100 (7) ◽  
pp. 870-880 ◽  
Author(s):  
B. T. Kalish ◽  
A. Matte ◽  
I. Andolfo ◽  
A. Iolascon ◽  
O. Weinberg ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Sickle Cell Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Transgenic Mouse Model ◽  
Cell Disease

scholarly journals Towards a transgenic mouse model of sickle cell disease: hemoglobin SAD.

1991 ◽  
Vol 10 (11) ◽  
pp. 3157-3165 ◽  
Author(s):  
M. Trudel ◽  
N. Saadane ◽  
M.C. Garel ◽  
J. Bardakdjian-Michau ◽  
Y. Blouquit ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Transgenic Mouse Model ◽  
Cell Disease

scholarly journals Microvascular response to cell free Hb infusion in transgenic mouse model of sickle cell anemia

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Amy G. Tsai ◽  
Pedro Cabrales ◽  
Mark A. Young ◽  
Robert M. Winslow ◽  
Marcos Intaglietta
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transgenic Mouse Model ◽  
Microvascular Response

scholarly journals Alterations in vascular reactivity in a transgenic mouse model of sickle cell trait

2020 ◽  
Vol 189 (4) ◽  
Author(s):  
Sarah Skinner ◽  
Kiao Ling Liu ◽  
Ming Lo ◽  
Audrey Josset‐Lamaugarny ◽  
Emmanuelle Charrin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Sickle Cell ◽  
Vascular Reactivity ◽  
Sickle Cell Trait ◽  
Transgenic Mouse Model
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