Jak2缺陷定义了确定性造血过程中的一个关键发育检查点。
Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis.
作者信息
Neubauer H, Cumano A, Müller M, Wu H, Huffstadt U, Pfeffer K
机构信息
Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Germany.
出版信息
Cell. 1998 May 1;93(3):397-409. doi: 10.1016/s0092-8674(00)81168-x.
Janus kinases (Jaks) play an important role in signal transduction via cytokine and growth factor receptors. A targeted inactivation of Jak2 was performed. Jak2-/- embryos are anemic and die around day 12.5 postcoitum. Primitive erythrocytes are found, but definitive erythropoiesis is absent. Compared to erythropoietin receptor-deficient mice, the phenotype of Jak2 deficiency is more severe. Fetal liver BFU-E and CFU-E colonies are completely absent. However, multilineage hematopoietic stem cells (CD34low, c-kit(pos)) can be found, and B lymphopoiesis appears intact. In contrast to IFNalpha stimulation, Jak2-/- cells do not respond to IFNgamma. Jak2-/- embryonic stem cells are competent for LIF signaling. The data provided demonstrate that Jak2 has pivotal functions for signal transduction of a set of cytokine receptors required in definitive erythropoiesis.
Janus激酶（Jaks）在通过细胞因子和生长因子受体进行的信号转导中发挥重要作用。对Jak2进行了靶向失活。Jak2基因敲除的胚胎出现贫血，并在妊娠12.5天左右死亡。可发现原始红细胞，但缺乏确定性红细胞生成。与促红细胞生成素受体缺陷小鼠相比，Jak2缺陷的表型更为严重。胎肝爆式红系集落形成单位（BFU-E）和红系集落形成单位（CFU-E）集落完全缺失。然而，可以发现多谱系造血干细胞（CD34低，c-kit阳性），并且B淋巴细胞生成似乎完整。与干扰素α刺激不同，Jak2基因敲除细胞对干扰素γ无反应。Jak2基因敲除的胚胎干细胞对白血病抑制因子（LIF）信号有反应。所提供的数据表明，Jak2对于确定性红细胞生成所需的一组细胞因子受体的信号转导具有关键作用。
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