title: Current progress in the production of recombinant human fibrinogen in the milk of transgenic animals.
abstract: The mammary gland of transgenic animals has several advantages for production of heterologous proteins including a high cell density that results in high concentrations of secreted protein. While the mammary gland appears to be able to secrete fully assembled recombinant human fibrinogen (rhfib) at 0.1 to 5 g/l levels, some unassembled rhfib chains are also secreted. Presently, the relationship between unassembled rhfib and the coordinated translation of each nascent rhfib polypeptide in the mammary epithelia is unknown. The secretion of fully and partially assembled rhfib is widely variable among mammalian cell lines and where previously no cell line has been shown to secrete beta chain alone. We have observed that mammary epithelia can secrete B beta chain into milk as well as immature forms of other recombinant proteins, suggesting it likely uses a different secretory pathway than does the liver. This difference in secretory behavior is possibly due to the natural design of milk, where the precise regulation of post translational modifications and intracellular pools of nascent polypeptides needed to achieve fibrinogen assembly may be less important to fulfill the nutritional function of most milk proteins.
authors.affiliation: Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg, USA. wvelande@vt.edu
authors.forename: S P
authors.initials: SP
authors.lastname: Butler
authors.forename: K
authors.initials: K
authors.lastname: van Cott
authors.forename: A
authors.initials: A
authors.lastname: Subrumanian
authors.forename: F C
authors.initials: FC
authors.lastname: Gwazduaskas
authors.forename: W H
authors.initials: WH
authors.lastname: Velander
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007782:Lactoglobulins / Q000235:genetics; D051379:Mice; D008892:Milk / Q000378:metabolism*; D008894:Milk Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D012756:Sheep
chemical_list: D007782:Lactoglobulins; D008894:Milk Proteins; D011994:Recombinant Proteins; C024471:whey acidic proteins; D005340:Fibrinogen