Transgenic Research

, Volume 15, Issue 5, pp 627–636

High Level Expression of Tissue-Nonspecific Alkaline Phosphatase in the Milk of Transgenic Rabbits

  • L. Bodrogi
  • R. Brands
  • W. Raaben
  • W. Seinen
  • M. Baranyi
  • D. Fiechter
  • Zs Bősze
Original Paper

Abstract

Alkaline phosphatase is a promising therapeutic agent in the Gram-negative bacterial lipopolysaccharide (LPS) mediated acute and chronic diseases. Contrary to other alkaline phosphatase isozymes, purified tissue-nonspecific alkaline phosphatase (TNAP) is not available in large quantities from tissue sources, which would enable to analyse its efficacy in animal sepsis models. Two transgenic rabbit lines were created by pronuclear microinjection with the whey acidic protein promoter-humanTNAP minigene (WAP-hTNAP). Lactating females of both lines produced biologically active human TNAP. As indicated by fractionation of milk samples the recombinant alkaline phosphatase was associated with the membrane of milk fat globules. Alkaline phosphatase enzymatic activity was two orders of magnitude higher compared to normal human serum levels. The demonstration that this TNAP is physiologically active would provide the clue to use transgenic animals as bioreactor for bulk production of the human tissue-nonspecific alkaline phosphatase in milk. This may be a valuable and possibly viable option with important implication in attenuating LPS mediated inflammatory responses.

Keywords

Tissue-nonspecific alkaline phosphatase LPS Transgenic rabbit milk Membrane associated recombinant protein 

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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • L. Bodrogi
    • 1
  • R. Brands
    • 2
  • W. Raaben
    • 3
  • W. Seinen
    • 2
  • M. Baranyi
    • 1
  • D. Fiechter
    • 3
  • Zs Bősze
    • 1
  1. 1.Department of Animal BiologyAgricultural Biotechnology CenterGödöllőHungary
  2. 2.IRASUniversity of UtrechtUtrechtThe Netherlands
  3. 3.AM-Pharma B.V. BunnikBunnikThe Netherlands

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