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Aerosol gene delivery to the murine lung is mouse strain dependent

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Abstract

The cationic polymer polyethylenimine (PEI) has been previously demonstrated to efficiently deliver genes to the lungs of mice in vivo via nebulization. Although within these studies various mouse strains were used in individual experiments, no direct comparison of gene delivery to different mouse strains via aerosol application has been published to date. With respect to the widespread use of mice as animal models of inherited and acquired diseases, such data could be of relevance to select the most appropriate mouse genetic background for preclinical mouse models. We investigated PEI-based aerosol gene delivery in two commonly used mouse strains, BALB/c and NMRI, and mixed 129/Sv × C57BL/6 mice. Gene expression in BALB/c mice was significantly 3.2- and 3.8-fold higher than in NMRI and 129/Sv × C57BL/6 mice, respectively. Lung deposition rates of radioactively labeled plasmid DNA (I123) complexed with PEI were not significantly different between each of the mouse strains. The kinetics of pDNA clearance from the lungs of BALB/c mice was slightly faster than from NMRI mice. Whereas gene expression increased until day 3 after treatment, the levels of pDNA decreased over the same period of time. Repeated aerosol application in a 3-day time interval could maintain gene expression at high levels compared with a single application. Furthermore, PEI–pDNA aerosol application led to reproducible gene expression in independent experiments. These data suggest that the genetic background of mice could be important 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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Acknowledgments

This work was supported by the German Federal Ministry of Education and Research in the program Nanotechnology, grants 13N8539 and 13N8538, and BioFuture (0311898).

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Author notes

  1. Carsten Rudolph

    Present address: Department of Pediatrics, University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany

Authors and Affiliations

  1. Department of Pediatrics, Ludwig-Maximilians University, 80337, Munich, Germany

    Petra Dames, Aurora Ortiz, Eugenia Lesina, Joseph Rosenecker & Carsten Rudolph

  2. Institute of Experimental Oncology and Therapy Research, Technical University of Munich, 81675, Munich, Germany

    Ulrike Schillinger & Christian Plank

  3. Department of Pharmacy, Free University of Berlin, Takustr. 3, 14166, Berlin, Germany

    Petra Dames & Carsten Rudolph

Authors
  1. Petra Dames
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  2. Aurora Ortiz
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  3. Ulrike Schillinger
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  4. Eugenia Lesina
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  5. Christian Plank
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  6. Joseph Rosenecker
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  7. Carsten Rudolph
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Correspondence to Carsten Rudolph.

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Dames, P., Ortiz, A., Schillinger, U. et al. Aerosol gene delivery to the murine lung is mouse strain dependent. J Mol Med 85, 371–378 (2007). https://doi.org/10.1007/s00109-006-0130-9

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  • DOI: https://doi.org/10.1007/s00109-006-0130-9

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