ROLE OF BHLH PROTEIN SCL IN HEMATOPOIETIC DEVELOPMENT

BHLH 蛋白 SCL 在造血发育中的作用

• 批准号: 6105666
• 负责人: STUART H ORKIN
• 金额: $ 9.06万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6105666
• 关键词: animal genetic material tag; complementary DNA; developmental genetics; embryogenesis; embryonic stem cell; erythropoiesis; gene interaction; gene targeting; genetic manipulation; hematology; hematopoiesis; laboratory mouse; molecular biology; nucleoproteins; phenotype; polymerase chain reaction; protein structure function; transcription factor; zebrafish

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.

红细胞发育所需的核调节蛋白则不是