Rescued mice with Hb E transgene-developed red cell changes similar to human beta-thalassemia/HbE disease.
A novel C57BL/6 transgenic murine model of HbE has been developed, and the heterotetrameric ((m)alpha2(h)beta(E)2) hemoglobin shows significant complementation of mild thalassemia phenotype in double heterozygous (beta(m+)beta(m-), beta(hE)) and homozygous knockout (beta(m-)beta(m-), beta(hE)) mice with 100% heterotetrameric hemoglobin. Lethal homozygous beta-thalassemic mice rescued by HbE transgenes mimic beta-thalassemia/HbE phenotype in human. Although anemia was not pronounced, other hematologic parameters were abnormally similar to beta-knockout mice. Flow cytometric study revealed a highly oxidative status in the red cells, but there were no marked changes in PS red cells and RBC vesicles. RBC life span and half-time of rescued red cells were shortened, indicating a rapid RBC destruction.
Wannasuphaphol
Bundit
B
Thalassemia Research Center, Institute of Science and Technology for Research and Development, Mahidol University, Phuttamonthon, Nakornpathom 73170, Thailand.
Kalpravidh
Ruchaneekorn
R
Pattanapanyasat
Kovit
K
Ioannau
Panos
P
Kuypers
Frans A
FA
Fucharoen
Suthat
S
Winichagoon
Pranee
P
D000818:Animals; D004195:Disease Models, Animal; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000737:chemistry; D004912:Erythrocytes / Q000473:pathology*; D005434:Flow Cytometry; D005816:Genetic Complementation Test; D005838:Genotype; D005914:Globins / Q000172:deficiency / Q000235:genetics; D006446:Hemoglobin E / Q000235:genetics*; D006454:Hemoglobins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008563:Membrane Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010641:Phenotype; D010718:Phosphatidylserines / Q000097:blood; D055503:Protein Multimerization; D021122:Protein Subunits; D019076:Transgenes; D017086:beta-Thalassemia / Q000097:blood* / Q000235:genetics
D006454:Hemoglobins; D008563:Membrane Lipids; D010718:Phosphatidylserines; D021122:Protein Subunits; D005914:Globins; D006446:Hemoglobin E