Radiation and haematopoiesis in Harwell steel mice.
Radiation and haematopoiesis in Harwell steel mice.
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哈威尔钢小鼠的辐射和造血。
DOI：
10.1080/09553008614551491
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
A. Searle
中科院分区：
文献类型：
--
作者：
J. Loutit;J. Peters;A. Searle
钢（Sl）小鼠的血液学信息主要限于Bar Harbor原种（WC.B6 F1）的Sl/Sld小鼠。因此，研究了两个Harwell等位基因SlgbH和Slcon。在稳定状态下，两种杂合子均中度贫血，纯合子Slcon和复合Slcon/SlgbH更是如此。在X射线照射的扰动下，Slcon/SlgbH显示半致死剂量（MLD）降低--6.5戈伊，Slcon/+和Slcon/Slcon的变化（7.5戈伊）与+/+、8戈伊相比稍小。在从亚致死剂量中恢复时，单杂合子、Wv双杂合子和化合物在恢复红细胞（RBC）计数方面没有延迟，如在典型W小鼠中所见（例如Wv/+、W/Wv）。对Slcon/Slcon和Slcon/SlgbH的影响与对Sl/Sld报告的不同之处在于，当用作致死性照射的骨髓受体时，它们显示脾集落的正常生长，它们支持植入骨髓的生长以形成辐射嵌合体。当Harwell steel小鼠为致死性辐照+/+小鼠的骨髓供体时，嵌合体最终不会贫血;当致死性辐照Harwell steel小鼠为+/+骨髓受体时，它们仍然是大细胞性贫血。人们推断，对于正常发育和正常RBC在稳态下的产生，红细胞需要由W基因座处的野生型等位基因决定的内在因素和由Sl基因座处的野生型等位基因决定的外在因素。任一位点的突变等位基因可决定大红细胞症。两个突变等位基因在任何一个位点仍然是有害的，往往是致命的。尽管突变体W等位基因也可能影响多能造血干细胞（HSC），导致X-照射时MLD降低，但Sl突变体的类似降低的MLD可能代表对造血干细胞产物的需求和消耗增加，而不是真正增加的放射敏感性，因为脾集落形成单位的Do对于Slcon/SlgbH与+/+小鼠相同。
Haematological information on steel (Sl) mice is limited largely to Sl/Sld mice of Bar Harbor stock (WC.B6 F1). Therefore, two Harwell alleles, SlgbH and Slcon, were investigated. In the steady state both heterozygotes were modestly anaemic, homozygous Slcon and compound Slcon/SlgbH more so. On perturbation by X-irradiation Slcon/SlgbH showed a decrease in median lethal dose (MLD)--6.5 Gy, Slcon/+ and Slcon/Slcon slightly less change (7.5 Gy) compared with +/+, 8 Gy. In recovery from sublethal doses single heterozygotes, double heterozygotes with Wv, and compounds showed no delay in restoration of the count of red blood corpuscles (RBC) such as that seen in typical W mice (e.g. Wv/+, W/Wv). Effects on Slcon/Slcon and Slcon/SlgbH differ from those reported for Sl/Sld in that they show normal growth of spleen colonies when used as lethally irradiated recipients of bone marrow, they support growth of implanted bone marrow to form radiation chimaeras. When Harwell steel mice are donors of bone marrow to lethally irradiated +/+ mice the chimaeras ultimately are not anaemic; when lethally irradiated Harwell steel mice are recipients of +/+ marrow they remain macrocytically anaemic. One deduces that, for normal development and production of normal RBC in the steady state, the erythron requires intrinsic factors determined by wild type alleles at the W locus and extrinsic factors determined by wild type alleles at the Sl locus. Mutant alleles at either locus may determine macrocytosis. Two mutant alleles at either locus are still more deleterious, often lethal. Whereas mutant W alleles may also influence the pluripotent haematopoietic stem cell (HSC) leading to reduced MLD on X-irradiation, a similarly reduced MLD for Sl mutants may represent an increased need for and consumption of products of the haematopoietic stem cells rather than truly increased radiosensitivity, since the Do for spleen colony-forming units is the same for Slcon/SlgbH as +/+ mice.