title: Production of functional human nerve growth factor from the saliva of transgenic mice by using salivary glands as bioreactors.
abstract: The salivary glands of animals have great potential to act as powerful bioreactors to produce human therapeutic proteins. Human nerve growth factor (hNGF) is an important pharmaceutical protein that is clinically effective in the treatment of many human neuronal and non-neuronal diseases. In this study, we generated 18 transgenic (TG) founder mice each carrying a salivary gland specific promoter-driven hNGF transgene. A TG mouse line secreting high levels of hNGF protein in its saliva (1.36 μg/mL) was selected. hNGF protein was successfully purified from the saliva of these TG mice and its identity was verified. The purified hNGF was highly functional as it displayed the ability to induce neuronal differentiation of PC12 cells. Furthermore, it strongly promoted proliferation of TF1 cells, above the levels observed with mouse NGF. Additionally, saliva collected from TG mice and containing unpurified hNGF was able to significantly enhance the growth of TF1 cells. This study not only provides a new and efficient approach for the synthesis of therapeutic hNGF but also supports the concept that salivary gland from TG animals is an efficient system for production of valuable foreign proteins.
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zeng
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Zicong
authors.initials: Z
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhao
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Guoling
authors.initials: G
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Gao
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Gelong
authors.initials: G
authors.lastname: Jiang
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Enqin
authors.initials: E
authors.lastname: Zheng
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Gengyuan
authors.initials: G
authors.lastname: Cai
authors.affiliation: Institute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, 96822, USA.|Manoa BioSciences, 1717 Mott-Smith Dr. #3213, Honolulu, 96822, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Moisyadi
authors.affiliation: Institute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, 96822, USA.
authors.forename: Johann
authors.initials: J
authors.lastname: Urschitz
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Yang
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Dewu
authors.initials: D
authors.lastname: Liu
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.|Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001681:Biological Assay; D019149:Bioreactors; D003433:Crosses, Genetic; D005260:Female; D016678:Genome; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D016716:PC12 Cells; D051381:Rats; D012463:Saliva / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism*; D019076:Transgenes
chemical_list: C502240:NGF protein, human; D020932:Nerve Growth Factor