E2A PROTEINS ARE REQUIRED FOR PROPER B-CELL DEVELOPMENT AND INITIATION OF IMMUNOGLOBULIN GENE REARRANGEMENTS
E2A PROTEINS ARE REQUIRED FOR PROPER B-CELL DEVELOPMENT AND INITIATION OF IMMUNOGLOBULIN GENE REARRANGEMENTS
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DOI：
10.1016/0092-8674(94)90077-9
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发表时间：
1994-12-02
期刊：
影响因子：
64.5
通讯作者：
MURRE, C
中科院分区：
文献类型：
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作者：
BAIN, G;MAANDAG, ECR;MURRE, C
E12和E47是两个螺旋-环-螺旋转录因子，通过E2A基因的选择性剪接而产生。两者都与免疫球蛋白基因表达的调节有关。我们现在已经通过基因打靶产生了E2A(-/-)小鼠。E2a缺失突变小鼠不能产生成熟的B细胞。B细胞发育受阻发生在早期阶段，因为在纯合子突变小鼠中没有检测到免疫球蛋白DJ重排。虽然免疫球蛋白胚系I-muRAG-1、mb-1、CD19和lambda 5转录本在E2A(-/-)小鼠胎肝中显著减少，但存在B29和Mu度转录本，但水平较低。此外，我们还发现E2A(-/-)小鼠胎肝中的Pax-5转录本显著减少。这些数据表明，E2A产物在早期B细胞分化中作为中央调节因子起着至关重要的作用。
E12 and E47 are two helix-loop-helix transcription factors that arise by alternative splicing of the E2A gene. Both have been implicated in the regulation of immunoglobulin gene expression. We have now generated E2A (-/-) mice by gene targeting. E2A-null mutant mice fail to generate mature B cells. The arrest of B cell development occurs at an early stage, since no immunoglobulin DJ rearrangements can be detected in homozygous mutant mice. While immunoglobulin germline I-mu RAG-1, mb-1, CD19, and lambda 5 transcripts are dramatically reduced in fetal livers of E2A (-/-) mice, B29 and mu degrees transcripts are present, but at lower levels. In addition, we show that Pax-5 transcripts are significantly reduced in fetal livers of E2A (-/-) mice. These data suggest a crucial role for E2A products as central regulators in early B cell differentiation.