title: Lactation performance of transgenic goats expressing recombinant human butyryl-cholinesterase in the milk.
abstract: The production of recombinant proteins in the milk of transgenic animals has attracted significant interest in the last decade, as a valuable alternative for the production of recombinant proteins that cannot be or are inefficiently produced using conventional systems based on microorganisms or animal cells. Several recombinant proteins of pharmaceutical and biomedical interest have been successfully expressed in high quantities (g/l) in the milk of transgenic animals. However, this productivity may be associated with a compromised mammary physiology resulting, among other things, from the extraordinary demand placed on the mammary secretory cells. In this study we evaluated the lactation performance of a herd of 50 transgenic goats expressing recombinant human butyryl-cholinesterase (rBChE) in the milk. Our findings indicate that high expression levels of rBChE (range 1-5 g/l) are produced in these animals at the expense of an impaired lactation performance. The key features characterizing these transgenic performances were the decreased milk production, the reduced milk fat content which was associated with an apparent disruption in the lipid secretory mechanism at the mammary epithelium level, and a highly increased presence of leukocytes in milk which is not associated with mammary infection. Despite of having a compromised lactation performance, the amount of rBChE produced per transgenic goat represents several orders of magnitude more than the amount of rBChE present in the blood of hundreds of human donors, the only other available source of rBChE for pharmaceutical and biodefense applications. As a result, this development constitutes another successful example in the application of transgenic animal technology.
authors.affiliation: PharmAthene Inc, 7150 Alexander Fleming, Montreal, QC, Canada, H4S 2C8. hbaldassarre@pharmathene.ca
authors.forename: Hernan
authors.initials: H
authors.lastname: Baldassarre
authors.forename: Duncan K
authors.initials: DK
authors.lastname: Hockley
authors.forename: Monique
authors.initials: M
authors.lastname: Doré
authors.forename: Eric
authors.initials: E
authors.lastname: Brochu
authors.forename: Bernard
authors.initials: B
authors.lastname: Hakier
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Vilceu
authors.initials: V
authors.lastname: Bordignon
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002091:Butyrylcholinesterase / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006041:Goats / Q000033:anatomy & histology / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007774:Lactation / Q000235:genetics* / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000201:enzymology / Q000473:pathology; D008892:Milk / Q000201:enzymology*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; D002091:Butyrylcholinesterase