Expression of Recombinant Human BChE in the Milk of Transgenic Mice

Abstract

Human butyrylcholinesterase (huBChE) has been successfully used as prophylaxis in animal models to prevent intoxication as a result of exposure to Organophosphate (OP) agents. Since large quantities of enzyme would be required for prophylaxis or treatment, we explored the production of recombinant huBChE (rc-huBChE) in the milk of transgenic animals. A DNA expression vector containing the huBChE cDNA under the control of the goat -casein promoter was used to generate transgenic mice lines. Milk collected from eight female mice contained active rc-huBChE at concentrations ranging from 0.15 to 1.8 g/L. The majority of the protein produced was found in the dimer form. In vitro nerve agent inhibition experiments demonstrated that rc-huBChE is similar to its human plasma counterpart in terms of broad-spectrum properties. The data from the expression of rc-huBChE in the milk of transgenic mice support the hypothesis that the mammary gland bioreactor can be used as a platform for the production of large quantities of active rc-huBChE.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA449754

Entities

People

  • A. Bellemare
  • A. Lazaris
  • C. N. Karatzas
  • D. E. Lenz
  • D. M. Cerasoli
  • M. Côté
  • M. Leduc
  • Yue Huang

Organizations

  • United States Army Medical Research Institute of Chemical Defense

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Animals
  • Biochemistry
  • Biotechnology
  • Chemistry
  • Deoxyribonucleic Acids
  • Enzyme Inhibitors
  • Enzymes
  • Genetically Modified Organisms
  • Glands
  • Inhibition
  • Mammary Glands
  • Manufacturing
  • Molecules
  • Nerve Agents
  • Production
  • Spreadsheet Software

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics
  • Neurotoxicology

Technology Areas

  • Biotechnology