Warren A J, Colledge W H, Carlton M B, Evans M J, Smith A J, Rabbitts T H
Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
Cell. 1994 Jul 15;78(1):45-57. doi: 10.1016/0092-8674(94)90571-1.
The LIM domain protein rbtn2 is associated with T cell acute leukemias. We demonstrate that rbtn2 is a nuclear protein expressed in the erythroid lineage in vivo, and using homologous recombination, we show that it is essential for erythroid development in mice. The homozygous rbtn2 null mutation leads to failure of yolk sac erythropoiesis and embryonic lethality around E10.5. Moreover, in vitro differentiation of yolk sac tissue from homozygous mutant mice and sequentially targeted double-mutant ES cells demonstrates a block to erythroid development. This shows a pivotal role for a LIM domain protein in lineage specification during mammalian development and suggests that RBTN2 and GATA-1 are critical at similar stages of erythroid differentiation.
LIM结构域蛋白rbtn2与T细胞急性白血病相关。我们证明rbtn2是一种在体内红系谱系中表达的核蛋白，并且通过同源重组，我们表明它对小鼠的红系发育至关重要。纯合的rbtn2无效突变导致卵黄囊红细胞生成失败以及在E10.5左右胚胎致死。此外，来自纯合突变小鼠的卵黄囊组织和顺序靶向的双突变胚胎干细胞的体外分化显示红系发育受阻。这表明一种LIM结构域蛋白在哺乳动物发育过程中的谱系特化中起关键作用，并表明RBTN2和GATA-1在红系分化的相似阶段至关重要。
