Studying human pathogens in animal models: Fine Tuning the Humanized Mouse

C Lassnig, Andreas Kolb, B Strobl, L Enjuanes, M Muller

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)803-806
    Number of pages4
    JournalTransgenic Research
    Volume14
    Issue number6
    DOIs
    Publication statusPublished - Dec 2005

    Keywords

    • aminopeptidase N
    • CD13
    • coronavirus
    • pathogen-receptor
    • Stat 1
    • transgenic mouse
    • transmissable gastroenteritis coronavirus
    • aminopeptidase-N
    • targeted disruption
    • enteric tropism
    • mice
    • infection
    • interferon
    • immunity
    • receptor
    • barrier

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