Miyakawa Y, Fukuchi Y, Ito M, Kobayashi K, Kuramochi T, Ikeda Y, Takebe Y, Tanaka T, Miyasaka M, Nakahata T, Tamaoki N, Nomura T, Ueyama Y, Shimamura K
Hu-Mouse Project, Eighth Laboratory, Kanagawa Academy of Science and Technology, Japan.
Br J Haematol. 1996 Dec;95(3):437-42. doi: 10.1046/j.1365-2141.1996.8012423.x.
Previous work has shown the usefulness of severe combined immunodeficient (SCID) mice as in vivo models for the growth of normal human haemopoietic cells and leukaemic cells. Many approaches have been made to improve the engraftment of human haemopoietic cells in SCID mice. We established transgenic mice producing human granulocyte-macrophage colony stimulating factor (hGM-CSF) with the homozygote of the scid gene. Endogenous serum hGM-CSF levels were detected by ELISA [mean 9585 pg/ml (line A, n = 4); mean 1610 pg/ml (line B, n = 4)]. Expression of hGM-CSF was observed in all organs tested including the heart, lung, liver, kidney, spleen, thymus, bone marrow and brain of hGM-CSF transgenic (hGMTg) mice. Morphological analysis of organs and peripheral blood cell counts showed no differences between hGMTg mice and their littermates. Murine Ba/F3 cells expressing functional hGM-CSF alpha beta receptor (BAF/alpha beta cells) could be successfully engrafted in hGMTg SCID mice. The cells invaded multiple organs and caused death within a few weeks of transplantation, although they infiltrated only the spleen of their littermates. These results showed that these hGM-CSF-producing SCID mice are useful as an in vivo assay system for investigating leukaemogenesis.
先前的研究表明，严重联合免疫缺陷（SCID）小鼠作为正常人类造血细胞和白血病细胞生长的体内模型具有实用性。人们已经采取了多种方法来提高人类造血细胞在SCID小鼠中的植入率。我们建立了携带scid基因纯合子并产生人类粒细胞-巨噬细胞集落刺激因子（hGM-CSF）的转基因小鼠。通过酶联免疫吸附测定法（ELISA）检测内源性血清hGM-CSF水平[平均9585 pg/ml（A系，n = 4）；平均1610 pg/ml（B系，n = 同样是4）]。在hGM-CSF转基因（hGMTg）小鼠的所有测试器官中均观察到hGM-CSF的表达，这些器官包括心脏、肺、肝脏、肾脏、脾脏、胸腺、骨髓和大脑。对器官的形态学分析和外周血细胞计数显示，hGMTg小鼠与其同窝出生的小鼠之间没有差异。表达功能性hGM-CSFαβ受体的鼠Ba/F3细胞（BAF/αβ细胞）能够成功植入hGMTg SCID小鼠体内。这些细胞侵入多个器官，并在移植后几周内导致死亡，而它们仅浸润同窝出生小鼠的脾脏。这些结果表明，这些产生hGM-CSF的SCID小鼠可作为研究白血病发生的体内检测系统。
