title: A galactopoiesis accordant yield of functional recombinant human factor IX from homozygous transgenic pigs requires a large amount of vitamin K supplementation.
abstract: Transgenic pigs failed to accord milk yield curve to lactate rhFIX-a vitamin K (VK) dependent protein even fed with VK enriched to 8 times higher than nutritional requirement. A further higher VK supplementation may be required. Homozygous transgenic sows (n = 4, 200 kg) at their 3rd nursing were divided into control and treatment groups and respectively received VK enriched and further menadione (soluble VK) supplemented diet (220 mg/kg VK enriched diet) for 33 days. At next lactation, control sows than received treatment and previous treated were fed on control diet. Results revealed that menadione treatment increased milk bioactivity of rhFIX from the 7th day of 73 to the 21st day of 153 IU/mL; it gradually decreased to 96 IU/mL on 35th day of lactation. Under control feeding, bioactivity remained relatively unchanged. However, milk rhFIX concentration and ratio of activated rhFIX responded little to the treatment. The menadione-induced bioactivity curve agrees with the known lactation pattern of sow means rhFIX secretion is still galactopoietic but requires high VK intake to show. The ineffectual VK spend on lactational carboxylation might be common in other mammary VK dependent expression system but can be effectively overcome by a high supplementation of menadione with a 5-folds improvement in quality.
authors.affiliation: Division of Animal Technology, Animal Technology Laboratories, Agriculture Technology Research Institute, No.1, Ln. 51, Dahu Rd., Xiangshan Dist., Hsinchu, 30093, Taiwan, ROC.
authors.forename: Chon-Ho
authors.initials: CH
authors.lastname: Yen
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, 1, Set. 1, Shen-Lung Rd, Ilan, 26041, Taiwan, ROC.
authors.forename: Tien-Shuh
authors.initials: TS
authors.lastname: Yang
authors.affiliation: Division of Animal Technology, Animal Technology Laboratories, Agriculture Technology Research Institute, No.1, Ln. 51, Dahu Rd., Xiangshan Dist., Hsinchu, 30093, Taiwan, ROC.
authors.forename: Yin-Shen
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Division of Animal Technology, Animal Technology Laboratories, Agriculture Technology Research Institute, No.1, Ln. 51, Dahu Rd., Xiangshan Dist., Hsinchu, 30093, Taiwan, ROC.
authors.forename: Meng-Hwan
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Division of Animal Technology, Animal Technology Laboratories, Agriculture Technology Research Institute, No.1, Ln. 51, Dahu Rd., Xiangshan Dist., Hsinchu, 30093, Taiwan, ROC.
authors.forename: Kuo-Cheng
authors.initials: KC
authors.lastname: Yu
authors.affiliation: Division of Animal Technology, Animal Technology Laboratories, Agriculture Technology Research Institute, No.1, Ln. 51, Dahu Rd., Xiangshan Dist., Hsinchu, 30093, Taiwan, ROC.
authors.forename: Chung-Lin
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Department of Animal Science, National Pingtung University of Science and Technology, No. 1, Sheufu Road, Neipu, Pingtung, 912, Taiwan, ROC.
authors.forename: How-Hong
authors.initials: HH
authors.lastname: Hsieh
authors.affiliation: Division of Animal Technology, Animal Technology Laboratories, Agriculture Technology Research Institute, No.1, Ln. 51, Dahu Rd., Xiangshan Dist., Hsinchu, 30093, Taiwan, ROC. cftu@mail.atri.org.tw.
authors.forename: Ching-Fu
authors.initials: CF
authors.lastname: Tu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019587:Dietary Supplements; D005164:Factor IX / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006720:Homozygote; D006801:Humans; D008892:Milk / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D034421:Sus scrofa / Q000235:genetics*; D014812:Vitamin K / Q000494:pharmacology*; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D014812:Vitamin K; D024483:Vitamin K 3; D005164:Factor IX
keywords: Galactopoiesis; Human factor IX; Transgenic sow; Vitamin K