Detection of endoplasmic reticulum stress markers and production enhancement treatments in transgenic goats expressing recombinant human butyrylcholinesterase

Compromised lactation physiology has been observed in transgenic animals, possibly due to the excessive demand placed by the expression of complex recombinant glycoproteins in the mammary gland. In previous studies we described lactation parameters and milk composition characteristics of transgenic goats expressing recombinant human butyrylcholinesterase in milk, and we showed evidence suggesting that lactation cessation could be associated with endoplasmic reticulum stress. We now report data from immunohistochemistry studies targeting activation transcription factor 6 and caspase 12, two signal transducers associated with endoplasmic reticulum stress, designed to further elucidate potential mechanisms responsible for the disruption in mammary epithelium function previously described. We found strong evidence of endoplasmic reticulum stress associated with the premature cessation of lactation. In addition, we utilized previously generated knowledge to design and test two treatments for enhanced productivity in transgenic goats. Pre-partum treatment with reserpine and dexamethasone to stimulate mammary priming for lactation resulted in a significant increase in milk production on day 1 (573 ± 350 vs. 93 ± 92 mL; P < 0.01), first week (8,832 ± 2,286 vs. 5,946 ± 2,039; P < 0.01) and the first month of lactation (42.5 ± 10 vs. 34.9 ± 6 kg; P < 0.05) compared to untreated controls. Mammary infusions with inosine during the early stages of lactation to promote mammary stem-cell proliferation also resulted in significantly increased milk production volumes, ranging from 26 to 200% more milk, in the treated glands compared to placebo.