Strain related variations in adenovirally mediated transgene expression from mouse hepatocytes in vivo: comparisons between immunocompetent and immunodeficient inbred strains

Gene Ther. 1995 Mar;2(2):151-5.


High efficiency gene transfer and gene expression in hepatocytes in vivo can be achieved using recombinant adenoviral vectors. However, the persistence of gene expression in different experimental animal models has been variable. To determine if similar differences could be observed in a single species, persistence of gene expression was studied in inbred strains of mice using a recombinant adenoviral vector that expresses human alpha 1-antitrypsin. Marked variability in the persistence of gene expression ranging from several weeks (C3H/HeJ and Balb/c) to more than 3 months [C57Bl/6, B10.A(2R) and B10.BR] was observed when this vector was transduced in different strains of inbred mice. This variability did not correlate with H-2 type. To evaluate the role of T and B cell immunity in the persistence of gene expression, congenic C3H-scid and Balb/c-scid mice were studied and found to have indefinite gene expression from transduced hepatocytes. These animals unlike their immunocompetent counter-parts were able to undergo secondary transduction of hepatocytes with a different recombinant adenoviral vector. These findings suggest that as yet unidentified genetic loci influence the persistence of adenovirus-mediated hepatic gene expression in vivo, and these effects are mediated at least in part, by the antigen specific immune system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology*
  • Crosses, Genetic
  • Gene Expression Regulation, Viral*
  • Genes, Synthetic
  • Genetic Vectors* / immunology
  • Genetic Vectors* / pharmacokinetics
  • Immunocompetence* / genetics
  • Liver / cytology
  • Liver / metabolism*
  • Liver / virology
  • Mice
  • Mice, Inbred BALB C / immunology*
  • Mice, Inbred C3H / immunology*
  • Mice, Inbred C57BL / immunology*
  • Mice, SCID / immunology*
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / genetics
  • Species Specificity
  • Time Factors
  • Transfection
  • alpha 1-Antitrypsin / biosynthesis*
  • alpha 1-Antitrypsin / genetics


  • Antibodies, Viral
  • Recombinant Fusion Proteins
  • alpha 1-Antitrypsin