Studying human pathogens in animal models: fine tuning the humanized mouse.

Studying human pathogens in animal models: fine tuning the humanized mouse.
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在动物模型中研究人类病原体:微调人性化小鼠。

DOI:
10.1007/s11248-005-1676-y
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发表时间:
2005-12
影响因子:
3
通讯作者:
Müller M
Müller M
中科院分区:
生物学4区
文献类型:
--
作者:
Lassnig C;Kolb A;Strobl B;Enjuanes L;Müller M

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人源化小鼠是在系统情况下研究人类病原体的重要工具。通过将病毒-细胞相互作用的人受体(氨肽酶N、APN、CD 13)基因转移到小鼠中,已经产生了人冠状病毒感染性疾病的动物模型。我们表明,在体外和体内感染的物种屏障不同的要求。转基因细胞对人冠状病毒HCoV-229 E感染敏感,证明病毒进入细胞需要hAPN。然而,转基因小鼠不能被感染,这表明对体内病毒易感性的额外要求。将hAPN转基因小鼠与干扰素无反应的Stat 1 −/−小鼠杂交,导致体外病毒复制显著增强,但体内病毒复制未检测到。人病毒对鼠细胞的适应导致人源化转基因小鼠的成功感染。未来的基因工程方法建议提供动物模型,更好地了解人类感染性疾病。
Humanized mice are crucial tools for studying human pathogens in systemic situations. An animal model of human coronavirus infectious disease has been generated by gene transfer of the human receptor for virus-cell interaction (aminopeptidase N, APN, CD13) into mice. We showed that in vitro and in vivo infections across the species barrier differ in their requirements. Transgenic cells were susceptible to human coronavirus HCoV-229E infection demonstrating the requirement of hAPN for viral cell entry. Transgenic mice, however, could not be infected suggesting additional requirements for in vivo virus susceptibility. Crossing hAPN transgenic mice with interferon unresponsive Stat1−/− mice resulted in markedly enhanced virus replication in vitro but did not result in detectable virus replication in vivo. Adaptation of the human virus to murine cells led to successful infection of the humanized transgenic mice. Future genetic engineering approaches are suggested to provide animal models for the better understanding of human infectious diseases.
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