title: Recombinant Derp5 allergen with αS1-casein signal peptide secreted in murine milk protects against dust mite allergen-induced airway inflammation.
abstract: Recent advances in recombinant technology make transgenic animals that produce pharmaceutical proteins in their milk more feasible. The group 5 allergen isolated from Dermatophagoides pteronyssinus (Derp5) is one of the most important dust mite allergens in humans. The aims of this study were to develop transgenic mice that could secrete recombinant Derp5-containing milk and to demonstrate that ingesting recombinant milk protects against allergic airway inflammation. Two transgenes were constructed separately. The α-LA-Derp5f transgene consisted of the bovine α-lactalbumin (α-LA) promoter and full-length Derp5 cDNA. The α-LA-CN-Derp5t transgene included the α-LA promoter, a leader sequence of αS1-casein (CN), and signal peptide-truncated Derp5 cDNA. Both species of transgenic mice were confirmed to have successful transgene integration and stable germline transmission. Western blot analysis of the milk obtained from the offspring of transgenic mice demonstrated that recombinant Derp5 was secreted successfully in the milk of αLA-CN-Derp5t transgenic mice but not in that of αLA-Derp5f transgenic mice. This study provides new evidence that transgenic mice can secrete recombinant Derp5 efficiently in milk by adding a signal peptide of αS1-casein. The antigenic activity of recombinant Derp5 milk was demonstrated to have a protective effect against allergic airway inflammation in a murine model in which the ingestion of recombinant Derp5-containing milk was used as pretreatment.
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Cheng Ching Hospital, Taichung 404, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 404, Taiwan.
authors.forename: Hsu-Chung
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Shun-Yuan
authors.initials: SY
authors.lastname: Pai
authors.affiliation: Department of Bioresources, Da-Yeh University, Changhwa 515, Taiwan.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Lai
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Tung-Chou
authors.initials: TC
authors.lastname: Tsai
authors.affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung 407, Taiwan.
authors.forename: Winston T K
authors.initials: WT
authors.lastname: Cheng
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Rong Hsing Research Center for Translational Medicine, and the iEGG Center, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: chchen1@dragon.nchu.edu.tw.
authors.forename: Chuan-Mu
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000235:genetics / Q000276:immunology*; D060829:Arthropod Proteins / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D002364:Caseins / Q000235:genetics / Q000276:immunology*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D007768:Lactalbumin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry* / Q000276:immunology; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D021382:Protein Sorting Signals / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D002364:Caseins; C451239:Dermatophagoides pteronyssinus antigen p 5; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D007768:Lactalbumin
keywords: Dermatophagoides pteronyssinus; Derp5 allergen; allergic airway inflammation; signal peptide; transgenic mice