Abstract
The cationic polymer polyethylenimine (PEI) has been widely used for efficient gene delivery to the lungs of mice via aerosol application. Various mouse strains have been used in these studies but direct comparisons between individual mouse strains have not been performed to date. However, due to the widespread use of mice as pre-clinical animal models of inherited and acquired diseases, investigation of interstrain variation of aerosol gene delivery could be of interest. PEI|[ndash]|based gene vectors were nebulized simultaneously to two commonly used mouse-strains, BALB/c and NMRI, and one transgenic heterozygous apoE-deficient mouse strain via an optimized whole body aerosol exposure device. Luciferase reporter gene expression measured in lung homogenates of BALB/c mice was significantly 3.2- and 3.8-fold higher than in NMRI and apoE- deficient mice, respectively. In order to assess dose-dependent effects due to different mouse strain-dependent deposition rates, radioactively-labeled plasmid DNA (I123) complexed with PEI was nebulized to the mice lungs. DNA deposition rates were not significantly different between each of the mouse-strains. These data suggest that the genetic background of mice could play an important role for nonviral aerosol gene delivery which should be considered in transgenic animal mouse models of inherited and acquired diseases for aerosol gene delivery studies.
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