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Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Studying human pathogens in animal models: fine tuning the humanized mouse
Caroline Lassnig1, Andreas Kolb, Birgit Strobl
1Department of Agrobiotechnology, IFA-Tulln, Institute of Biotechnology in Animal Production, University of Natural Resources and Applied Life Sciences, Austria.
Transgenic Research
|November 30, 2005
Summary
Humanized mice expressing human aminopeptidase N (hAPN) were susceptible to human coronavirus HCoV-229E infection in vitro. However, these mice required further adaptation for in vivo infection, highlighting species-specific barriers.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Humanized mice are essential for studying human pathogens.
- Developing animal models for human coronaviruses is critical for understanding infectious diseases.
Purpose of the Study:
- To create a humanized mouse model for human coronavirus (HCoV) infection.
- To investigate the requirements for HCoV entry and replication across species barriers.
Main Methods:
- Gene transfer of human aminopeptidase N (hAPN, CD13) into mice to create transgenic models.
- In vitro infection assays using transgenic cells and mice.
- In vivo infection studies with transgenic mice, including crossing with Stat1(-/-) mice.
- Viral adaptation studies to overcome species-specific barriers.
Main Results:
- Transgenic cells expressing hAPN were susceptible to HCoV-229E, confirming hAPN's role in viral entry.
- Transgenic mice expressing hAPN alone were not susceptible to HCoV-229E infection in vivo, indicating additional host factors are required.
- Crossing hAPN transgenic mice with Stat1(-/-) mice enhanced in vitro replication but did not enable in vivo infection.
- Adaptation of HCoV-229E to murine cells was necessary for successful infection of humanized transgenic mice.
Conclusions:
- hAPN is necessary but not sufficient for HCoV-229E infection in vivo.
- Infection across species barriers involves complex host-pathogen interactions beyond receptor binding.
- Further genetic engineering and viral adaptation are needed to establish robust animal models for human coronavirus diseases.
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