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.