T细胞白血病LIM蛋白Lmo2对成年小鼠的造血作用是必需的。
The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis.
作者信息
Yamada Y, Warren A J, Dobson C, Forster A, Pannell R, Rabbitts T H
机构信息
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3890-5. doi: 10.1073/pnas.95.7.3890.
Abstract
The LIM-finger protein Lmo2, which is activated in T cell leukemias by chromosomal translocations, is required for yolk sac erythropoiesis. Because Lmo2 null mutant mice die at embryonic day 9-10, it prevents an assessment of a role in other stages of hematopoiesis. We have now studied the hematopoietic contribution of homozygous mutant Lmo2 -/- mouse embryonic stem cells and found that Lmo2 -/- cells do not contribute to any hematopoietic lineage in adult chimeric mice, but reintroduction of an Lmo2-expression vector rescues the ability of Lmo2 null embryonic stem cells to contribute to all lineages tested. This disruption of hematopoiesis probably occurs because interaction of Lmo2 protein with factors such as Tal1/Scl is precluded. Thus, Lmo2 is necessary for early stages of hematopoiesis, and the Lmo2 master gene encodes a protein that has a central and crucial role in the hematopoietic development.
摘要
LIM指蛋白Lmo2在T细胞白血病中因染色体易位而被激活，它是卵黄囊红细胞生成所必需的。由于Lmo2基因敲除的突变小鼠在胚胎第9至10天死亡，因此无法评估其在造血其他阶段的作用。我们现在研究了纯合突变Lmo2 -/- 小鼠胚胎干细胞的造血贡献，发现Lmo2 -/- 细胞在成年嵌合小鼠中对任何造血谱系都没有贡献，但重新引入Lmo2表达载体可挽救Lmo2基因敲除胚胎干细胞对所有测试谱系的贡献能力。造血功能的这种破坏可能是因为Lmo2蛋白与Tal1/Scl等因子的相互作用被阻断。因此，Lmo2是造血早期阶段所必需的，Lmo2主基因编码一种在造血发育中起核心和关键作用的蛋白质。
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