ABSENCE OF BLOOD FORMATION IN MICE LACKING THE T-CELL LEUKEMIA ONCOPROTEIN TAL-1/SCL
ABSENCE OF BLOOD FORMATION IN MICE LACKING THE T-CELL LEUKEMIA ONCOPROTEIN TAL-1/SCL
复制标题
DOI：
10.1038/373432a0
复制
发表时间：
1995-02-02
期刊：
影响因子：
64.8
通讯作者：
ORKIN, SH
中科院分区：
文献类型：
--
作者：
SHIVDASANI, RA;MAYER, EL;ORKIN, SH
与恶性肿瘤相关的染色体易位常常导致编码转录因子的基因表达失调(1)。在人类t细胞白血病中，这些调节因子属于不同的蛋白家族，通常可能广泛表达（例如Ttg-1/rbtn1， Ttg-2/rbtn2）（2'3），完全在造血系统外表达（例如Hox11）(4)，或特异性地在造血细胞和其他选定位点表达（例如tal-1/ SCL， lyl-1）（5,6）。T细胞内的异常表达被认为干扰了正常的成熟程序。tal-1（也称为SCL）是急性t细胞白血病中最常激活的基因（7,8），它编码造血发育的候选调节因子(9)，一种碱性螺旋-环-螺旋蛋白(5)，与关键的肌源性（10）和神经源性（11）因子相关。在这里，我们通过对小鼠的靶向基因破坏（12）表明，tal-1对体内胚胎血液形成至关重要。就胚胎红细胞生成而言，tal-1缺陷类似于红细胞转录因子GATA-(13,14)或LIM蛋白rbtn2（15）的缺失。从tal-1卵黄囊中培养的髓系细胞大量减少表明在髓系红细胞或多潜能祖细胞水平上存在更广泛的缺陷。
CHROMOSOMAL translocations associated with malignancies often result in deregulated expression of genes encoding transcription factors(1). In human T-cell leukaemias such regulators belong to diverse protein families and may normally be expressed widely (for example, Ttg-1/rbtn1, Ttg-2/rbtn2)(2'3), exclusively outside the haematopoietic system (for example, Hox11)(4), or specifically in haematopoietic cells and other selected sites (for example, tal-1/ SCL, lyl-1)(5,6). Aberrant expression within T cells is thought to interfere with programmes of normal maturation. The most frequently activated gene in acute T-cell leukaemias, tal-1 (also called SCL)(7,8), encodes a candidate regulator of haematopoietic development(9), a basic-helix-loop-helix protein(5), related to critical myogenic(10) and neurogenic(11) factors. Here we show by targeted gene disruption in mice(12) that tal-1 is essential for embryonic blood formation in vivo. With respect to embryonic erythropoiesis, tal-1 deficiency resembles loss of the erythroid transcription factor GATA-(13,14) or the LIM protein rbtn2(15). Profound reduction in myeloid cells cultured in vivo from tal-1 null yolk sacs suggests a broader defect manifest at the myelo-erythroid or multipotential progenitor cell level.