ROLE OF BHLH PROTEIN SCL IN HEMATOPOIETIC DEVELOPMENT
ROLE OF BHLH PROTEIN SCL IN HEMATOPOIETIC DEVELOPMENT
批准号:
6105666
负责人:
STUART H ORKIN
金额:
$9.06万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-09-15 至 1999-08-31
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
中文摘要
红系细胞发育所需的核调节蛋白质不是
完全定义。在其他发育系统中,
螺旋-环-螺旋(bHLH)家族通常参与指定细胞命运。
bHLH因子被称为SCL(干细胞白血病)(也称为tal-
1/TCL 5)是在红系细胞中发挥重要作用的潜在候选者。
发展在这个项目中,小鼠SCL基因将被灭活,
胚胎干细胞中的基因靶向,以及缺乏的纯合子小鼠
将生成SCL。这些小鼠的表型将是
在整个胚胎发生和成年生活中具有特征(如果可行的话)。在
此外,SCL缺陷纯合的ES细胞将从
单敲除细胞,以评估造血和红系细胞
体外发育如果体外或体内的表型不
在没有SCL的情况下,系统地寻找潜在的
多余的蛋白质将进行,并涉及杂交育种的SCL
具有其它bHLH敲除的杂合子(例如Lyl)。进一步
研究SCL在血细胞发育中的作用,
将与核心B合作分离cDNA克隆,
用于检测正常斑马鱼SCL RNA表达模式
发育,并在异常造血发育所表现出的
无血突变体和其他斑马鱼突变体,
全世界的调查员。通过对小鼠SCL和
斑马鱼,这种蛋白质在红细胞发育中的作用应该是
确立了习
英文摘要
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.
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依托单位:
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批准号:9066186
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资助金额:$68.41万
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财政年份:2014
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依托单位:
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资助金额:$67.58万
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财政年份:2014
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依托单位:
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资助金额:$66.23万
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财政年份:2014
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财政年份:2009
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依托单位:
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资助金额:$113.46万
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财政年份:2009
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依托单位:
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资助金额:$109.42万
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财政年份:2009
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负责人:STUART H ORKIN
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依托单位:
Research Training in Pediatric Oncology
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批准号:8103031
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项目类别:
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资助金额:$46.36万
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财政年份:2009
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负责人:STUART H ORKIN
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依托单位:
Research Training in Pediatric Oncology
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项目类别:
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资助金额:$52.35万
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财政年份:2009
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依托单位:
Research Training in Pediatric Oncology
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项目类别:
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资助金额:$50.35万
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财政年份:2009
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依托单位:
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资助金额:$51.94万
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财政年份:2009
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负责人:STUART H ORKIN
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依托单位:
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