The human alpha-1-antitrypsin gene is efficiently expressed from two tissue-specific promotors in transgenic mice

Nucleic Acids Res. 1987 Sep 25;15(18):7519-29. doi: 10.1093/nar/15.18.7519.

Abstract

Alpha 1-antitrypsin (alpha 1AT) present in large amounts in human serum and synthesized predominantly in hepatocytes, is the most abundant protease inhibitor and alpha 1AT mutant proteins are associated with hereditary disorders. To investigate the regulation of the normal human alpha 1AT gene, we have microinjected fertilized mouse eggs with a 17.5 kb DNA fragment containing the entire gene with 7 kb 5' and 0.3 kb 3' flanking sequences. We show that this DNA fragment contains all the information for efficient, accurate and tissue-specific expression. High serum concentration of the human protein was found in three independent transgenic mouse lines. The human alpha 1AT RNA is transcribed efficiently in liver, kidney and macrophages and we demonstrate that two different promoters are used for the expression in liver and macrophages of the transgenic mice.

Publication types

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

MeSH terms

  • Animals
  • DNA, Recombinant
  • Female
  • Gene Expression Regulation
  • Humans
  • Kidney / metabolism
  • Liver / metabolism
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Organ Specificity
  • Promoter Regions, Genetic*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics*
  • alpha 1-Antitrypsin / biosynthesis
  • alpha 1-Antitrypsin / genetics*

Substances

  • DNA, Recombinant
  • Recombinant Proteins
  • alpha 1-Antitrypsin