NOD/SCID/γcnull mouse:: an excellent recipient mouse model for engraftment of human cells
NOD/SCID/γcnull mouse:: an excellent recipient mouse model for engraftment of human cells
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DOI：
10.1182/blood-2001-12-0207
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发表时间：
2002-11-01
期刊：
影响因子：
20.3
通讯作者：
Nakahata, T
中科院分区：
文献类型：
--
作者：
Ito, M;Hiramatsu, H;Nakahata, T
为了建立更合适的异种移植动物受体，我们将C57BL/ 6j - γ (c)（null）小鼠与NOD/ shid - SCID小鼠进行8次回交交配，产生了NOD SCID/ γ (c)（null）严重联合免疫缺陷（SCID）突变和白细胞介素- 2rγ (IL-2Rgamma)等位基因突变(γ (c)（null）的双纯合小鼠。将人脐带血CD34（+）细胞移植到该品系中，其外周循环、脾脏和骨髓的移植率明显高于抗亚洲毒瘤GM1抗体处理的NOD/ shiz - SCID小鼠或β 2-微球蛋白缺陷NOD/LtSz-scid （NOD/SCID/ β 2- 2m(null)）小鼠，后者的NK细胞活性与NOD/SCID/ γ (c)（null）小鼠一样完全缺陷。外周血单个核细胞腹腔移植后，腹水中成熟细胞的植入率同样高。除了高移植率外，还观察到多系细胞分化。此外，即使是1 × 10(2)个CD34（+）细胞也可以在该菌株中生长和分化。这些结果表明NOD/SCIO/ γ (c)（null）小鼠是异种移植的优越动物受体，对人类干细胞试验尤其有价值。为了阐明NOD/SCID/ γ (c)（null）小鼠高移植率的机制，我们比较了3株小鼠在单核细胞增生李斯特菌抗原刺激下脾脏细胞的细胞因子产生情况。NOD/SCID/ γ (c)（null）小鼠脾脏的树突状细胞产生的干扰素- γ与其他2种小鼠的结果相比明显受到抑制。研究表明，多种免疫功能障碍，包括细胞因子产生能力，以及T、B和NK细胞的功能不全，可能导致NOD/SCID/ γ (c)（null）小鼠中异种移植物的高移植水平。(C) 2002年由美国血液病学会出版。
To establish a more appropriate animal recipient for xenotransplantation, NOD SCID/gamma(c)(null) mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interieukin-2Rgamma (IL-2Rgamma) allelic mutation (gamma(c)(null)) were generated by 8 backcross matings of C57BL/6J-gamma(c)(null) mice and NOD/Shi-scid mice. When human CD34(+) cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi-scid mice treated with anti-asialo GM1 antibody or in the beta2-microglobulindeficient NOD/LtSz-scid (NOD/SCID/beta2m(null)) mice, which were as completely defective in NK cell activity as NOD/SCID/gamma(c)(null) mice. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. In addition to the high engraftment rate, multilineage cell differentiation was also observed. Further, even 1 x 10(2) CD34(+) cells could grow and differentiate in this strain. These results suggest that NOD/SCIO/gamma(c)(null) mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/gamma(c)(null) mice, cytolkine production of spleen cells stimulated with Listeria monocytogenes antigens was compared among these 3 strains of mice. The interferon-gamma production from dendritic cells from the NOD/SCID/gamma(c)(null) mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/gamma(c)(null) mice. (C) 2002 by The American Society of Hematology.