The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse
The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse
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DOI：
10.1002/j.1460-2075.1996.tb00787.x
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发表时间：
1996-08-15
期刊：
影响因子：
11.4
通讯作者：
Begley, CG
中科院分区：
文献类型：
--
作者：
Robb, L;Elwood, NJ;Begley, CG
scl基因无效突变的纯合性导致小鼠妊娠中期胚胎死亡，原因是原始造血发育失败。虽然这一观察确立了scl基因产物在原始造血中的作用，但scl缺失胚胎的死亡排除了对scl在以后造血发育中作用的分析。为了解决这个问题，我们创建了scl基因纯合无效突变（scl（-/-））的胚胎干细胞系，并使用这些细胞系来获得嵌合小鼠。对嵌合小鼠的分析表明，scl（-/-）胚胎干细胞对所有非造血组织有实质性贡献，但对任何造血谱系没有贡献。这些观察结果揭示了scl基因产物在确定性造血中的关键作用。用SCL（-/-）胚胎干细胞进行的体外分化试验表明，在该系统中，SCL基因产物也是造血细胞形成所必需的。
Homozygosity for a null mutation in the scl gene causes mid-gestational embryonic lethality in the mouse due to failure of development of primitive hematopoiesis. Whilst this observation established the role of the scl gene product in primitive hematopoiesis, the death of the scl null embryos precluded analysis of the role of scl in later hematopoietic development. To address this question, we created embryonic stem cell lines with a homozygous null mutation of the scl gene (scl(-/-)) and used these lines to derive chimeric mice. Analysis of the chimeric mice demonstrates that the scl(-/-) embryonic stem cells make a substantial contribution to all non-hematopoietic tissues but do not contribute to any hematopoietic lineage, These observations reveal a crucial role for the scl gene product in definitive hematopoiesis, In addition, in vitro differentiation assays with scl(-/-) embryonic stem cells showed that the scl gene product was also required for formation of hematopoietic cells in this system.