Wannasuphaphol Bundit, Kalpravidh Ruchaneekorn, Pattanapanyasat Kovit, Ioannau Panos, Kuypers Frans A, Fucharoen Suthat, Winichagoon Pranee
Thalassemia Research Center, Institute of Science and Technology for Research and Development, Mahidol University, Phuttamonthon, Nakornpathom 73170, Thailand.
Ann N Y Acad Sci. 2005;1054:407-16. doi: 10.1196/annals.1345.049.
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.
已构建出一种新型的C57BL/6 HbE转基因小鼠模型，杂合四聚体（(m)α2(h)β(E)2）血红蛋白在双杂合（β(m+)β(m-)，β(hE)）和纯合敲除（β(m-)β(m-)，β(hE)）小鼠中显示出对轻度地中海贫血表型的显著互补作用，其中血红蛋白100%为杂合四聚体。由HbE转基因拯救的致死性纯合β地中海贫血小鼠模拟了人类β地中海贫血/HbE表型。尽管贫血并不明显，但其他血液学参数与β敲除小鼠异常相似。流式细胞术研究显示红细胞处于高度氧化状态，但磷脂酰丝氨酸（PS）红细胞和红细胞囊泡没有明显变化。拯救的红细胞的红细胞寿命和半衰期缩短，表明红细胞破坏迅速。
