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
    • Department of Animal BiologyAgricultural Biotechnology Center
  • R. Brands
    • IRASUniversity of Utrecht
  • W. Raaben
    • AM-Pharma B.V. Bunnik
  • W. Seinen
    • IRASUniversity of Utrecht
  • M. Baranyi
    • Department of Animal BiologyAgricultural Biotechnology Center
  • D. Fiechter
    • AM-Pharma B.V. Bunnik
    • Department of Animal BiologyAgricultural Biotechnology Center
Original Paper

DOI: 10.1007/s11248-006-9015-5

Cite this article as:
Bodrogi, L., Brands, R., Raaben, W. et al. Transgenic Res (2006) 15: 627. doi:10.1007/s11248-006-9015-5


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.


Tissue-nonspecific alkaline phosphataseLPSTransgenic rabbit milkMembrane associated recombinant protein
Download to read the full article text

Copyright information

© Springer Science+Business Media B.V. 2006