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

Ulrich Rüther, Marco Tripodi, Riccardo Cortcsc, Erwin F. Wagner

Research output: Contribution to journalArticle

Abstract

α-1-antitrypsin (α-1AT) present in large amounts in human serum and. synthesized predominantly in hepatocytes, is the most abundant protease inhibitor and α-1AT mutant proteins are associated with heriditary disorders. To investigate the regulation of the normal human α-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 α-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.

Original languageEnglish
Pages (from-to)7519-7529
Number of pages11
JournalNucleic Acids Research
Volume15
Issue number18
DOIs
Publication statusPublished - Sep 25 1987

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)
  • Genetics

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