ROLE OF BHLH PROTEIN SCL IN HEMATOPOIETIC DEVELOPMENT

红系发育所需的核调节蛋白不是 完全定义好了。在其他发育系统中，碱性的蛋白质 螺旋-环-螺旋(BHLH)家族经常参与决定细胞命运。 BHLH因子被称为SCL(干细胞白血病)(也被称为TAL- 1/TCL5)可能在红系疾病中发挥重要作用 发展。在这个项目中，小鼠的SCL基因将通过以下方式失活 胚胎干细胞和纯合子缺陷小鼠的基因打靶 将生成SCL的。这些小鼠的表型将是 在胚胎发育和成年生活(如果可行)过程中表现出的特征。在……里面 此外，SCL缺乏症的纯合子ES细胞将从 单个基因敲除细胞用于评价造血系和红系 体外发育。如果体外或体内的表型不是 在没有SCL的情况下，系统地寻找潜在的 将进行多余的蛋白质，并涉及SCL的杂交育种 杂合子与其他bHLH基因敲除(如Lyl)。为了进一步 斑马鱼SCL在血细胞发育中的作用 将与Core B合作分离cDNA克隆，这将是 用于检测正常斑马鱼中SCL RNA的表达模式 发育，以及在异常的造血发育中表现的 无血突变体和其他斑马鱼突变体将由 世界各地的调查人员。通过对小鼠和小鼠SCL的联合研究 斑马鱼这种蛋白质在红系发育中的作用应该是 已经成立了。

The nuclear regulatory proteins required for erythroid development are not entirely defined. In other developmental systems proteins of the basic helix-loop-helix (bHLH) family are often involved in specifying cell fate. The bHLH factor known as SCL (stem cell leukemia) (also known as tal- 1/TCL5) is a potential candidate for an important role in erythroid development. In this project the murine SCL gene will be inactivated by gene targeting in embryonic stem cells, and mice homozygous for deficiency of SCL will be generated. The phenotype of these mice will be characterized throughout embryogenesis and adult life (if viable). In addition, ES cells homozygous for SCL deficiency will be generated from single knock-out cells in order to assess hematopoietic and erythroid development in vitro. If the phenotypes in vitro or in vivo are not striking in the absence of SCL, a systematic search for potentially redundant proteins will be undertaken, and involve cross-breeding of SCL heterozygotes with other bHLH knock-outs (e.g. Lyl). To further investigate the role of SCL in blood cell development, a zebrafish SCL cDNA clone will be isolated in collaboration with Core B, which will be used to examine the pattern of SCL RNA expression in normal zebrafish development, and in abnormal hematopoietic development exhibited by the bloodless mutant and other zebrafish mutants to be provided from investigators worldwide. Through combined study of SCL in mice and zebrafish the role of this protein in erythroid development should be established.