A common human β globin splicing mutation modeled in mice
A common human β globin splicing mutation modeled in mice
复制标题
DOI：
10.1182/blood.v91.6.2152.2152_2152_2156
复制
发表时间：
1998-03-15
期刊：
影响因子：
20.3
通讯作者：
Maeda, N
中科院分区：
文献类型：
--
作者：
Lewis, J;Yang, BL;Maeda, N
β 1VS-2-654 C-->T突变约占中国南方β地中海贫血突变的20%;它引起异常RNA剪接并导致β（0）地中海贫血。为了提供用于测试校正剪接缺陷的疗法的动物模型，我们已经使用了在鼠胚胎干细胞中基因靶向的“插头和插座”方法，以用人β 1VS-2-654基因的单拷贝替换两个（顺式）鼠成体β珠蛋白基因。没有纯合子小鼠出生后存活。携带这种突变基因的杂合子小鼠产生的小鼠β珠蛋白链减少，而不产生人类β珠蛋白，并具有中度形式的β地中海贫血。杂合子显示出与其人类对应物相同的异常剪接，并提供了用于测试在RNA或DNA水平上校正剪接缺陷的疗法的动物模型。(C)1998年，美国血液学会。
The beta lVS-2-654 C-->T mutation accounts for approximately 20% of beta thalassemia mutations in southern China; it causes aberrant RNA splicing and leads to beta(0) thalassemia. To provide an animal model for testing therapies for correcting splicing defects, we have used the "plug and socket" method of gene targeting in murine embryonic stem cells to replace the two (cis) murine adult beta globin genes with a single copy of the human beta lVS-2-654 gene. No homozygous mice survive postnatally. Heterozygous mice carrying this mutant gene produce reduced amounts of the mouse beta globin chains and no human beta globin, and have a moderate form of beta thalassemia. The heterozygotes show the same aberrant splicing as their human counterparts and provide an animal model for testing therapies to correct splicing defects at either the RNA or DNA level. (C) 1998 by The American Society of Hematology.