High expression of human pBs and a-globins in transgenic mice: Hemoglobin composition and hematological consequences
High expression of human pBs and a-globins in transgenic mice: Hemoglobin composition and hematological consequences
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转基因小鼠中人类 pB 和 a-珠蛋白的高表达：血红蛋白组成和血液学后果
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通讯作者：
F. Costantini
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作者：
M. Fabry;R. Nagel;Agathe PACHNISt;S. Suzuka;F. Costantini
建立转基因小鼠系（aHpS_11;其中H是人α-珠蛋白），其中人α s和人α 2珠蛋白基因共整合到小鼠基因组中，每个基因与β-珠蛋白基因座控制区连接。在正常的遗传背景下，转基因小鼠产生36%的人β-珠蛋白链，α 1/β PS比为1.3。通过将转基因小鼠与携带小鼠pJm 4 or-珠蛋白基因缺失的突变小鼠交配，获得了更高水平的Ps。pmajor缺失（a.8S [[pMDj; MD，小鼠缺失）杂合小鼠的PJS为54%，all/ps比值为1.0; pmajor缺失（aHps[pMDDj]）纯合小鼠的fis为72.5%，aH/ps比值为0.73。因为小鼠α链抑制血红蛋白（Hb）S聚合，我们将小鼠培育为小鼠α-珠蛋白缺失的杂合性。这些小鼠（aHpIS[aMDpMDDj]）具有0.89的增加的H/ps比率，但表达65%的ps。人类基因的表达治愈了与鼠pmajor缺失相关的地中海贫血表型。转基因aVIHS[pMDD]小鼠具有
A line of transgenic mice (aHpS_1l; where a H is human a-globin) was created in which the human s and human a2 globin genes, each linked to the 13-globin locus control region, were cointegrated into the mouse genome. On a normal genetic background, the transgenic mice produced 36% human (s-globin chains with an al/yps ratio of 1.3. Higher levels of Ps were achieved by breeding the transgenic mice with mutant mice carrying a mouse pJm4or-globin gene deletion. Mice heterozygous for the pmajor deletion (a .8S[[pMDj; MD, mouse deletion) had 54% PJS with an all/ps ratio of 1.0; mice homozygous for the pmajor deletion (aHps[pMDDj) had 72.5% fis and an aH/ps ratio of 0.73. Because mouse a chains inhibit hemoglobin (Hb) S polymerization, we bred the mice to heterozygosity for a mouse a-globin deletion. These mice (aHpIS[aMDpMDDj) had an increased a H/ps ratio of 0.89 but expressed 65% ps. Expression of the human genes cured the thalassemic phenotype associated with the murine pmajor deletion. Transgenic aVIHS[pMDD] mice had