title: Transgenic mice expressing yeast CUP1 exhibit increased copper utilization from feeds.
abstract: Copper is required for structural and catalytic properties of a variety of enzymes participating in many vital biological processes for growth and development. Feeds provide most of the copper as an essential micronutrient consumed by animals, but inorganic copper could not be utilized effectively. In the present study, we aimed to develop transgenic mouse models to test if copper utilization will be increased by providing the animals with an exogenous gene for generation of copper chelatin in saliva. Considering that the S. cerevisiae CUP1 gene encodes a Cys-rich protein that can bind copper as specifically as copper chelatin in yeast, we therefore constructed a transgene plasmid containing the CUP1 gene regulated for specific expression in the salivary glands by a promoter of gene coding pig parotid secretory protein. Transgenic CUP1 was highly expressed in the parotid and submandibular salivary glands and secreted in saliva as a 9-kDa copper-chelating protein. Expression of salivary copper-chelating proteins reduced fecal copper contents by 21.61% and increased body-weight by 12.97%, suggesting that chelating proteins improve the utilization and absorbed efficacy of copper. No negative effects on the health of the transgenic mice were found by blood biochemistry and histology analysis. These results demonstrate that the introduction of the salivary CUP1 transgene into animals offers a possible approach to increase the utilization efficiency of copper and decrease the fecal copper contents.
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, PR China, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, PR China.
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Xie
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, PR China, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, PR China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, PR China, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, PR China.
authors.forename: Zhenliang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, PR China, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Liao
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, PR China, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, PR China.
authors.forename: Xiangzhe
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, PR China, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, PR China.
authors.forename: Qishan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, PR China, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, PR China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000821:Animal Feed; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001835:Body Weight; D003300:Copper / Q000378:metabolism*; D017931:DNA Primers; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism
chemical_list: C500769:CUP1-1 protein, S cerevisiae; D017931:DNA Primers; D003300:Copper; D008668:Metallothionein