Characterization of novel regulators of erythropoiesis

成熟的红细胞和白细胞由成人骨髓中的造血干细胞发育而来。红细胞的产生主要由激素促红细胞生成素（epo）控制。重组形式的这种激素的可用性有助于治疗多种由肾衰竭、恶性肿瘤和艾滋病引起的贫血。在此之前，我们已经发现蛋白质Lyn必须存在于原始红细胞中，促红细胞生成素才能刺激它们成为成熟的功能细胞。我们在红细胞中发现了六种与林恩相互作用的分子。我们已经证明了一种叫做HS1的分子对单个红细胞的促红细胞生成素功能很重要，现在我们计划在整个动物中研究它的功能，包括缺乏HS1基因的小鼠。我们还发现一种叫做Trip1的分子对红细胞的发育很重要。有趣的是，这种分子还能与甲状腺激素受体相互作用，影响促红细胞生成素和甲状腺激素对红细胞发育的影响。这两种激素之间的相互作用将在正常小鼠和缺乏甲状腺激素受体基因的小鼠的细胞和整个动物水平上进行更详细的研究。我们分离到的第三个Lyn结合分子是一个新基因，我们根据其相关分子将其命名为锚蛋白重复蛋白。这个基因在红细胞中表达，我们的目标是研究它在这些细胞的发育中起什么作用。第四个基因也是新基因，与另一个名为AFAP-110的基因密切相关，后者可以对细胞结构产生影响。它在红细胞结构中的作用也将被研究。最后，我们确定的最后两个分子都是新的，与任何其他已知的蛋白质无关。如上所述，我们将研究这两种分子对红细胞发育的影响。

Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature functional cells. We have identified six molecules which interact with Lyn in red blood cells. We have shown that amolecule called HS1 is important for epo function in individual red blood cells and now we plan to investigate its functions in whole animals, including mice that lack the HS1 gene. We have also shown that a molecule called Trip1 is important for red blood cell development. Interestingly, this molecule also interacts with the thyroid hormone receptor and can influence the effects of epo and thyroid hormone on red blood cell development. The interplay between these two hormones will be looked at in more detail both at the cell and whole animal levels in normal mice and those lacking the thyroid hormone receptor gene. The third Lyn binding molecule we isolated is a novel gene-we have named it ankyrin repeat protein in line with the molecules it is related to. This gene is expressed in red blood cells and we aim to investigate what role it plays in the development of these cells. The fourth gene is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Its role in red blood cell structure will also be investigated. Finally, the last two molecule we have identified are both novel and are unrelated to any other known proteins. As above, the effects of these two molecules on red blood cell development will be investigated.