Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/25260
標題: 水蛭素基因轉殖母豬乳腺與乳汁蛋白質體之研究
A study on the mammary gland and milk proteome of Hirudin transgenic sows
作者: 李東仁
Lee, Tung-Jen
關鍵字: Hirudin;水蛭素;trangenic;sows;mammary gland;milk;proteome;基因轉殖;母豬;乳腺;乳汁;蛋白質體
出版社: 動物科學系所
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摘要: 
水蛭素(Hirudin)為一有效之凝血素(thrombin)抑制物,在止血作用(hemostasis)與血栓形成(thrombosis)扮演關鍵角色。水蛭素基因轉殖豬之產製將可生產重組水蛭素(recombinant Hirudin; rHirudin)供醫療應用。本研究之目的為分析豬隻乳腺與乳汁蛋白質體並評估水蛭素轉殖基因是否影響水蛭素基因轉殖母豬乳腺與乳汁蛋白質表現。乳腺與乳汁樣品採自分娩當天之水蛭素基因轉殖與非基因轉殖母豬,取均質後乳腺及脫脂後乳汁之可溶性蛋白質供雙向電泳分析,電泳膠片以colloidal Coomassie blue染色後掃描供影像分析或挖取蛋白質點供身份鑑定用。在乳腺樣品共挖取242個蛋白質點進行胜肽質量指紋分析,身份鑑定成功之172個蛋白質點分別屬於99個不同蛋白質,此等蛋白質可分類為下列功能群:能量路徑與代謝(25.3%)、蛋白質代謝(21.2%)、細胞生長與維持(15.2%)、運輸(12.1%)、免疫反應(9.1%)、細胞聯繫與訊息傳遞(9.1%)、核酸代謝與調節(3%)、細胞凋亡(2%)及未知功能蛋白質(3%)等。基因轉殖與非基因轉殖母豬乳腺蛋白質點以Melanie 3影像分析軟體進行定量,在所有定量分析的147個乳腺蛋白質點中有9個蛋白質點之表現量在基因轉殖與非基因轉殖母豬間具顯著差異(P<0.05),其中在基因轉殖母豬乳腺表現量下降之蛋白質點為凝溶膠蛋白(gelsolin)及4個血紅素(hemoglobin) isoforms,表現增加之蛋白質點為異檸檬酸去氫酶1 (isocitrate dehydrogenase 1)、絲胺酸胜肽酶抑制物(serpin peptidase inhibitor)及2個未知身份蛋白質。在乳汁樣品共挖取293個蛋白質點進行身份鑑定,身份鑑定成功之140個蛋白質點分別屬於45個不同蛋白質,此等蛋白質可依功能分為免疫反應(31.1%)、運輸(28.9%)、蛋白質代謝(8.9%)、細胞聯繫與訊息傳遞(8.9%)、細胞生長與維持(8.9%)、能量路徑與代謝(4.4%)、核酸代謝與調節(2.2%)、細胞凋亡(2.2%)及未知功能蛋白質(4.4%)等。在所有定量的85個乳汁蛋白質點中有4個蛋白質點在基因轉殖與非基因轉殖母豬間具顯著差異(P<0.05),其中在基因轉殖母豬乳汁表現下降的蛋白質點為血紅素結合蛋白(haptoglobin)及2個未知蛋白質,另1個在基因轉殖母豬乳汁表現量上升蛋白質點則為未知身份蛋白質。綜合以上,本研究已初步建立豬乳腺與乳汁雙向電泳蛋白質參考圖譜,定量分析發現在水蛭素基因轉殖與非基因轉殖母豬間乳腺與乳汁分別有9個與4個蛋白質點之表現差異顯著,此等差異表現蛋白質之確切生理意義及未知身份蛋白質點之身份仍有待進一步研究。

Hirudin is a potent inhibitor of thrombin and plays a key role in hemostasis and thrombosis. Transgenic pigs carrying Hirudin gene have been generated for producing recombinant Hirudin in milk. The recombinant Hirudin will be applicable therapeutically. The purposes of this study were to analyze the porcine mammary gland and milk proteome and to evaluate whether Hirudin transgene affects the expression levels of mammary gland and milk proteins in Hirudin transgenic sows. Mammary gland and milk samples were collected from two Hirudin transgenic and two non-transgenic sows on the day of farrowing. Tissue samples were homogenized and soluble proteins were isolated for analysis. Milk proteins were collected after removing milk fat. Soluble proteins from mammary gland and milk samples were assayed by 2-DE and stained with colloidal Coomassie blue. Gels were scanned for further image analysis or subjected to excising protein spots for identification. In mammary gland, a total of 242 protein spots were subjected to peptide mass fingerprinting for identification. There were 172 protein spots corresponding to 99 different proteins were successfully identified. The identified proteins were categorized into functional groups of energy pathways/metabolism (25.3%), protein metabolism (21.2%), cell growth/maintenance (15.2%), transport (12.1%), immune response (9.1%), cell communication/signal transduction (9.1%), nucleic acid metabolism/regulation (3%), apoptosis (2%), and unknown function (3%). A total of 147 protein spots on all mammary gland 2-DE gels were quantified using Melanie 3 software. The levels of nine protein spots were significantly different between transgenic and non-transgenic sows (P<0.05). The down-regulated proteins in the mammary gland of transgenic sows were gelsolin and four isoforms of hemoglobin. Isocitrate dehydrogenase, serpin peptidase inhibitor and the other two unidentified protein spots were up-regulated in the mammary gland of transgenic sows. In milk, a total of 293 protein spots were subjected to identification. There were 140 protein spots identified and were corresponding to 45 different proteins. The identified proteins were categorized into functional groups of immune response (31.1%), transport (28.9%), protein metabolism (8.9%), cell communication/signal transduction (8.9%), cell growth/maintenance (8.9%), energy pathways/metabolism (4.4%), nucleic acid metabolism/regulation (2.2%), apoptosis (2.2%), and unknown function (4.4%). A total of 85 milk protein spots on all milk 2-DE gels were quantified. The levels of four protein spots were significantly different between milk from transgenic and non-transgenic sows (P<0.05). Haptoglobin and two unidentified proteins were down-regulated in milk from transgenic sows. The identity of the up-regulated protein in milk from transgenic sows remains unidentified. In summary, this study established 2-DE protein reference maps of porcine mammary gland and milk and found that there were nine mammary gland protein spots and four milk protein spots differed between Hirudin transgenic and non-transgenic sows, respectively. The exact physiological relevance of the differentially expressed proteins and the identities of those unidentified protein spots in transgenic pigs require further elucidation.
URI: http://hdl.handle.net/11455/25260
其他識別: U0005-2807200902510000
Appears in Collections:動物科學系

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