Production of Recombinant Human Von Willebrand Factor in the Milk of Transgenic Pigs

• Published in: Journal of Reproduction and Development Vol. 55; no. 5; pp. 484 - 490
• Main Authors: LEE, Hyun-Gi, LEE, Hwi-Cheul, KIM, Sung Woo, LEE, Poongyeon, CHUNG, Hak-Jae, LEE, Yun-Keun, HAN, Joo-Hee, HWANG, In-Sul, YOO, Jong-Il, KIM, Yong-Kook, KIM, Hun-Taek, LEE, Hoon-Taek, CHANG, Won-Kyong, PARK, Jin-Ki
• Format: Journal Article
• Language: English
• Published: Japan THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT 2009
• Subjects: Animals; Animals, Genetically Modified; Factor VIII - metabolism; Female; Gene Expression; Humans; Mammary gland; Mammary Glands, Animal - metabolism; Microinjection; Milk - metabolism; Organ Culture Techniques; Protein Binding; Recombinant Proteins - genetics; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sus scrofa; Transgenic pig; Von Willebrand factor; von Willebrand Factor - genetics; von Willebrand Factor - isolation & purification; von Willebrand Factor - metabolism
• ISSN: 0916-8818; 1348-4400
• DOI: 10.1262/jrd.20212

Von Willebrand factor (vWF), a large multimeric glycoprotein present in blood plasma, is a blood protein of the coagulation system. It is defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura-hemolytic uremic syndrome and heyde's syndrome. We have developed a line of transgenic swine harboring recombinant human von Willebrand factor (rhvWF) cDNA through microinjection of fertilized one-cell pig zygotes. Expression of rhvWF in the mammary gland and secretion of rhvWF into the milk of the transgenic swine were confirmed by immunohistochemical and western blot analyses, respectively, and rhvWF proteins were detected in milk from all lactating founder females at concentrations that were 28- to 56-folds greater than that in circulating human plasma. The amino acid sequence of rhvWF protein in the transgenic pig milk matched that of vWF produced from human blood plasma. This study provides evidence that production of rhvWF from transgenic pig milk is a potentially valuable technology and can be used as a cost-effective alternative in clinical applications.