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Publication : A new human DSG2-transgenic mouse model for studying the tropism and pathology of human adenoviruses.

First Author  Wang H Year  2012
Journal  J Virol Volume  86
Issue  11 Pages  6286-302
PubMed ID  22457526 Mgi Jnum  J:186087
Mgi Id  MGI:5431017 Doi  10.1128/JVI.00205-12
Citation  Wang H, et al. (2012) A new human DSG2-transgenic mouse model for studying the tropism and pathology of human adenoviruses. J Virol 86(11):6286-302
abstractText  We have recently reported that a group of human adenoviruses (HAdVs) uses desmoglein 2 (DSG2) as a receptor for infection. Among these are the widely distributed serotypes HAdV-B3 and HAdV-B7, as well as a newly emerged strain derived from HAdV-B14. These serotypes do not infect rodent cells and could not up until now be studied in small-animal models. We therefore generated transgenic mice containing the human DSG2 locus. These mice expressed human DSG2 (hDSG2) at a level and in a pattern similar to those found for humans and nonhuman primates. As an initial application of hDSG2-transgenic mice, we used a green fluorescent protein (GFP)-expressing HAdV-B3 vector (Ad3-GFP) and studied GFP transgene expression by quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry subsequent to intranasal and intravenous virus application. After intranasal application, we found efficient transduction of bronchial and alveolar epithelial cells in hDSG2-transgenic mice. Intravenous Ad3-GFP injection into hDSG2-transgenic mice resulted in hDSG2-dependent transduction of epithelial cells in the intestinal and colon mucosa. Our findings give an explanation for clinical symptoms associated with infection by DSG2-interacting HAdVs and provide a rationale for using Ad3-derived vectors in gene therapy.
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