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

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Abstract

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.

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References

  • Baldassarre H, Karatzas CN (2004) Advanced assisted reproduction technologies (ART) in goats. Anim Reprod Sci 82–83:255–266

    Article  PubMed  Google Scholar 

  • Baldassarre H, Wang B, Keefer CL, Lazaris A, Karatzas CN (2004) State of the art in the production of transgenic goats. Reprod Fertil Dev 16:465–470

    Article  PubMed  CAS  Google Scholar 

  • Baldassarre H, Rao KM, Neveu N, Brochu E, Begin I, Behboodi E, Hockley DK (2007) Laparoscopic ovum pick-up followed by in vitro embryo production for the reproductive rescue of aged goats of high genetic value. Reprod Fertil Dev 19:612–616

    Article  PubMed  CAS  Google Scholar 

  • Baldassarre H, Hockley DK, Dore M, Brochu E, Hakier B, Zhao X, Bordignon V (2008a) Lactation performance of transgenic goats expressing recombinant human butyryl-cholinesterase in the milk. Transgenic Res 17:73–84

    Article  PubMed  CAS  Google Scholar 

  • Baldassarre H, Hockley DK, Olaniyan B, Brochu E, Zhao X, Mustafa A, Bordignon V (2008b) Milk composition studies in transgenic goats expressing recombinant human butyrylcholinesterase in the mammary gland. Transgenic Res 17:863–872

    Article  PubMed  CAS  Google Scholar 

  • Baldassarre H, Schirm M, Deslauriers J, Turcotte C, Bordignon V (2009) Protein profile and alpha-lactalbumin concentration in the milk of standard and transgenic goats expressing recombinant human butyrylcholinesterase. Transgenic Res 18:621–632

    Article  PubMed  CAS  Google Scholar 

  • Burdon TG, Demmer J, Clark AJ, Watson CJ (1994) The mammary factor MPBF is a prolactin-induced transcriptional regulator which binds to STAT factor recognition sites. FEBS Lett 350:177–182

    Article  PubMed  CAS  Google Scholar 

  • Capuco AV, Ellis S (2005) Bovine mammary progenitor cells: current concepts and future directions. J Mammary Gland Biol Neoplasia 10:5–15

    Article  PubMed  CAS  Google Scholar 

  • Capuco AV, Evock-Clover CM, Minuti A, Wood DL (2009) In vivo expansion of the mammary stem/progenitor cell population by xanthosine infusion. Exp Biol Med (Maywood) 234:475–482

    Article  CAS  Google Scholar 

  • Collier RJ, Bauman DE, Hays RL (1977) Effect of reserpine on milk production and serum prolactin of cows hormonally induced into lactation. J Dairy Sci 60:896–901

    Article  PubMed  CAS  Google Scholar 

  • Cudna RE, Dickson AJ (2003) Endoplasmic reticulum signaling as a determinant of recombinant protein expression. Biotechnol Bioeng 81:56–65

    Article  PubMed  CAS  Google Scholar 

  • Davis SR, Welch RA, Pearce MG, Peterson AJ (1983) Induction of lactation in nonpregnant cows by estradiol-17 beta and progesterone from an intravaginal sponge. J Dairy Sci 66:450–457

    Article  PubMed  CAS  Google Scholar 

  • Doctor BP, Saxena A (2005) Bioscavengers for the protection of humans against organophosphate toxicity. Chem Biol Interact 157–158:167–171

    Article  PubMed  Google Scholar 

  • Hart IC, Morant SV (1980) Roles of prolactin, growth hormone, insulin and thyroxine in steroid-induced lactation in goats. J Endocrinol 84:343–351

    Article  PubMed  CAS  Google Scholar 

  • Houdebine LM (2009) Production of pharmaceutical proteins by transgenic animals. Comp Immunol Microbiol Infect Dis 32:107–121

    Article  PubMed  Google Scholar 

  • Huang YJ, Huang Y, Baldassarre H, Wang B, Lazaris A, Leduc M, Bilodeau AS, Bellemare A, Cote M, Herskovits P, Touati M, Turcotte C, Valeanu L, Lemee N, Wilgus H, Begin I, Bhatia B, Rao K, Neveu N, Brochu E, Pierson J, Hockley DK, Cerasoli DM, Lenz DE, Karatzas CN, Langermann S (2007) Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning. Proc Natl Acad Sci U S A 104:13603–13608

    Article  PubMed  CAS  Google Scholar 

  • Keefer CL (2004) Production of bioproducts through the use of transgenic animal models. Anim Reprod Sci 82–83:5–12

    Article  PubMed  Google Scholar 

  • Kensinger RS, Bauman DE, Collier RJ (1979) Season and treatment effects on serum prolactin and milk yield during induced lactation. J Dairy Sci 62:1880–1888

    Article  PubMed  CAS  Google Scholar 

  • Lee AS (2001) The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci 26:504–510

    Article  PubMed  CAS  Google Scholar 

  • Little E, Ramakrishnan M, Roy B, Gazit G, Lee AS (1994) The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications. Crit Rev Eukaryot Gene Expr 4:1–18

    PubMed  Google Scholar 

  • Peel CJ, Taylor JW, Robinson IB, Hooley RD (1979) The use of oestrogen, progesterone and reserpine in the artificial induction of lactation in cattle. Aust J Biol Sci 32:251–259

    PubMed  CAS  Google Scholar 

  • Salama AA, Caja G, Albanell E, Carne S, Casals R, Such X (2007) Mammogenesis and induced lactation with or without reserpine in nulliparous dairy goats. J Dairy Sci 90:3751–3757

    Article  PubMed  CAS  Google Scholar 

  • Schroder M (2006) The unfolded protein response. Mol Biotechnol 34:279–290

    Article  PubMed  CAS  Google Scholar 

  • Schroder M (2008) Endoplasmic reticulum stress responses. Cell Mol Life Sci 65:862–894

    Article  PubMed  CAS  Google Scholar 

  • Schroder M, Kohno K (2007) Recent advances in understanding the unfolded protein response. Antioxid Redox Signal 9:2241–2244

    Article  PubMed  CAS  Google Scholar 

  • Wheeler MB, Walters EM, Clark SG (2003) Transgenic animals in biomedicine and agriculture: outlook for the future. Anim Reprod Sci 79:265–289

    Article  PubMed  CAS  Google Scholar 

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Baldassarre, H., Deslauriers, J., Neveu, N. et al. Detection of endoplasmic reticulum stress markers and production enhancement treatments in transgenic goats expressing recombinant human butyrylcholinesterase. Transgenic Res 20, 1265–1272 (2011). https://doi.org/10.1007/s11248-011-9493-y

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  • DOI: https://doi.org/10.1007/s11248-011-9493-y

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