Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation.

Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation.
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DOI:
10.1016/j.clim.2009.12.008
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发表时间:
2010-04
期刊:
Clinical immunology (Orlando, Fla.)
影响因子:
--
通讯作者:
Greiner DL
Greiner DL
中科院分区:
其他
文献类型:
--
作者:
Brehm MA;Cuthbert A;Yang C;Miller DM;DiIorio P;Laning J;Burzenski L;Gott B;Foreman O;Kavirayani A;Herlihy M;Rossini AA;Shultz LD;Greiner DL

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通过用人血淋巴细胞或组织移植免疫缺陷小鼠而产生的“人源化”小鼠模型是一种新兴技术,在多个生物医学学科中具有广泛的吸引力。然而,希望利用具有移植的功能性人免疫系统的人源化小鼠的研究人员面临着无数的变量要考虑。在这项研究中,我们使用三种携带IL 2 r γ无效突变的免疫缺陷小鼠品系:NOD-scid IL 2 r γnull、NOD-Rag 1 null IL 2 r γnull和BALB/c-Rag 1 null IL 2 r γnull小鼠,分析HSC植入方法。策略比较了静脉内注射到成年小鼠和心内和肝内注射到新生小鼠后来自脐带血的人HSC的植入。我们观察到,新生儿受体表现出增强植入相比,成人受体。与方案或受体年龄无关,与BALB/c株相比,两种免疫缺陷NOD株均支持增强的造血细胞植入。我们的数据定义了建立人源化小鼠模型以研究人类免疫的关键参数。
“Humanized” mouse models created by engraftment of immunodeficient mice with human hematolymphoid cells or tissues are an emerging technology with broad appeal across multiple biomedical disciplines. However, investigators wishing to utilize humanized mice with engrafted functional human immune systems are faced with a myriad of variables to consider. In this study, we analyze HSC engraftment methodologies using three immunodeficient mouse strains harboring the IL2rγnull mutation; NOD-scid IL2rγnull, NOD-Rag1null IL2rγnull, and BALB/c-Rag1null IL2rγnull mice. Strategies compared engraftment of human HSC derived from umbilical cord blood following intravenous injection into adult mice and intracardiac and intrahepatic injection into newborn mice. We observed that newborn recipients exhibited enhanced engraftment as compared to adult recipients. Irrespective of the protocol or age of recipient, both immunodeficient NOD strains support enhanced hematopoietic cell engraftment as compared to the BALB/c strain. Our data define key parameters for establishing humanized mouse models to study human immunity.
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