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, Z. Bösze

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)627-636
Number of pages10
JournalTransgenic Research
Volume15
Issue number5
DOIs
Publication statusPublished - Oct 2006

Fingerprint

Alkaline Phosphatase
alkaline phosphatase
Milk
rabbits
genetically modified organisms
Rabbits
milk
lipopolysaccharides
Lipopolysaccharides
acute course
lactating females
transgenic animals
Genetically Modified Animals
fat globules
tissues
Microinjections
Bioreactors
Acute Disease
bioreactors
whey

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Plant Science
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Biotechnology
  • Food Science

Cite this

High level expression of tissue-nonspecific alkaline phosphatase in the milk of transgenic rabbits. / Bodrogi, L.; Brands, R.; Raaben, W.; Seinen, W.; Baranyi, M.; Fiechter, D.; Bösze, Z.

In: Transgenic Research, Vol. 15, No. 5, 10.2006, p. 627-636.

Research output: Contribution to journalArticle

Bodrogi, L. ; Brands, R. ; Raaben, W. ; Seinen, W. ; Baranyi, M. ; Fiechter, D. ; Bösze, Z. / High level expression of tissue-nonspecific alkaline phosphatase in the milk of transgenic rabbits. In: Transgenic Research. 2006 ; Vol. 15, No. 5. pp. 627-636.
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