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- Title
128. Evaluation of a CD46-Transgenic Mouse as a Model for Adenovirus Distribution and Expression.
- Authors
Andersson, Emma; Grundberg, Ida; Edlund, Karin; Wadell, Göran
- Abstract
Wild-type mice do not naturally express CD46, a protein expressed on all nucleated human cells and proposed to be the functional receptor for Adenoviruses (Ad) of species B. Mice do however express a homologue to human coxsackievirus-adenovirus receptor (CAR), the common Ad receptor for several serotypes, including Ad5p (species C) and Ad4 (species E).Here we evaluate a mouse model transgenic for human CD46 in which the protein, similar to the human situation, is expressed on all cells, compared with a wt strain of the same background.We have focused on the uncommon human adenoviruses Ad11p (species B), Ad4 and the chimpanzee adenovirus Cv23 (species E), in comparison with the thoroughly investigated and endemic Ad5p upon which most gene therapy research and trials have been based. These serotypes are of great interest as vector candidates as they are distinct from Ad5p to which a large part of the population is immune.Upon intravenous injection Ad5p was localised and accumulated mainly in the liver of both transgenic- and control mice in accordance with previous studies. Cv23 was found at low levels mostly in liver and spleen early after virus infusion but was then rapidly cleared from blood and tissues. Interestingly, the distribution pattern of Ad4 was very similar to that of Cv23 but not of Ad5p. This was surprising since both Ad4 and Ad5p are CAR binding viruses. Ad11p on the other hand had a unique distribution pattern in the CD46- transgenic mice not seen in wt mice indicating utilisation of CD46. This transgenic mouse seems to be a functioning model for studies of species B Ad, which in wt mouse strains may underestimate the transduction capacity. These findings emphasize the need for biologically relevant model systems that are required for further development of Ad11p as a vector and for thorough investigation of the distribution and effects of various vector candidates.Molecular Therapy (2006) 13, S52–S52; doi: 10.1016/j.ymthe.2006.08.149
- Subjects
TRANSGENIC mice; ADENOVIRUSES; COXSACKIEVIRUSES; INTRAVENOUS therapy; GENE therapy
- Publication
Molecular Therapy, 2006, Vol 13, pS52
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.149