Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoproteinCIII
Hypertriglyceridemia has recently been considered to be an independent risk factor for coronary heart disease, in which apolipoprotein (Apo)CIII is one of the major contributory factors, as it is strongly correlated with plasma triglyceride levels. Although ApoCIII transgenic mice have been generate...
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| Veröffentlicht in: | The FEBS journal 2012-01, Vol.279 (1), p.91-99 |
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| creator | Wei, Jingyuan Ouyang, Hongsheng Wang, Yuhui Pang, Daxin Cong, Nathan X Wang, Tiedong Leng, Bingfeng Li, Dong Li, Xiaoping Wu, Rong Ding, Yu Gao, Fei Deng, Yanhong Liu, Bo Li, Ziyi Lai, Liangxue Feng, Haihua Liu, George Deng, Xuming |
| description | Hypertriglyceridemia has recently been considered to be an independent risk factor for coronary heart disease, in which apolipoprotein (Apo)CIII is one of the major contributory factors, as it is strongly correlated with plasma triglyceride levels. Although ApoCIII transgenic mice have been generated as an animal model for the study of hypertriglyceridemia, the features of lipoprotein metabolism in mice differ greatly from those in humans. Because of the great similarity between pigs and humans with respect to lipid metabolism and cardiovascular physiology, we generated transgenic miniature pigs expressing human ApoCIII by the transfection of somatic cells combined with nuclear transfer. The expression of human ApoCIII was detected in the liver and intestine of the transgenic pigs. As compared with nontransgenic controls, transgenic pigs showed significantly increased plasma triglyceride levels (83±36 versus 38±4mg·dL-1, P |
| doi_str_mv | 10.1111/j.1742-4658.2011.08401.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_1399903009</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2536403581</sourcerecordid><originalsourceid>FETCH-LOGICAL-p609-3b9c437b009caec6c0257d01c09f389a8467598f144f9ff4e2e65b72beb0307a3</originalsourceid><addsrcrecordid>eNpdjktLxDAUhYMoOI7-h-DKTetNkz6ylOKjMOBmFu6GNHPbydAmNUlhxl9vQXHh2dwD5-OeQwhlkLJFj8eUlSJLRJFXaQaMpVAJYOnpgqz-gss_Lz6uyU0IRwCeCylXZKwPyisd0ZsvFY2z1HVU0cN5Qh-96YezXqI9jkbT6JUNPdrFjsYaFWePdDI9Hd0eB4qnyWMIxvb0MI_KUjW5wUxu8i6isXXTNLfkqlNDwLvfuybbl-dt_ZZs3l-b-mmTTAXIhLdSC162AFIr1IWGLC_3wDTIjldSVaIoc1l1TIhOdp3ADIu8LbMWW-BQKr4mDz9vl-rPGUPcjSZoHAZl0c1hx7iUckFBLuj9P_ToZm-XcTvJoAIQkvFvFqRscA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>910800491</pqid></control><display><type>article</type><title>Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoproteinCIII</title><source>Wiley Journals</source><source>Wiley Online Library Free Content</source><source>IngentaConnect Free/Open Access Journals</source><source>Free Full-Text Journals in Chemistry</source><creator>Wei, Jingyuan ; Ouyang, Hongsheng ; Wang, Yuhui ; Pang, Daxin ; Cong, Nathan X ; Wang, Tiedong ; Leng, Bingfeng ; Li, Dong ; Li, Xiaoping ; Wu, Rong ; Ding, Yu ; Gao, Fei ; Deng, Yanhong ; Liu, Bo ; Li, Ziyi ; Lai, Liangxue ; Feng, Haihua ; Liu, George ; Deng, Xuming</creator><creatorcontrib>Wei, Jingyuan ; Ouyang, Hongsheng ; Wang, Yuhui ; Pang, Daxin ; Cong, Nathan X ; Wang, Tiedong ; Leng, Bingfeng ; Li, Dong ; Li, Xiaoping ; Wu, Rong ; Ding, Yu ; Gao, Fei ; Deng, Yanhong ; Liu, Bo ; Li, Ziyi ; Lai, Liangxue ; Feng, Haihua ; Liu, George ; Deng, Xuming</creatorcontrib><description>Hypertriglyceridemia has recently been considered to be an independent risk factor for coronary heart disease, in which apolipoprotein (Apo)CIII is one of the major contributory factors, as it is strongly correlated with plasma triglyceride levels. Although ApoCIII transgenic mice have been generated as an animal model for the study of hypertriglyceridemia, the features of lipoprotein metabolism in mice differ greatly from those in humans. Because of the great similarity between pigs and humans with respect to lipid metabolism and cardiovascular physiology, we generated transgenic miniature pigs expressing human ApoCIII by the transfection of somatic cells combined with nuclear transfer. The expression of human ApoCIII was detected in the liver and intestine of the transgenic pigs. As compared with nontransgenic controls, transgenic pigs showed significantly increased plasma triglyceride levels (83±36 versus 38±4mg·dL-1, P <0.01) when fed a chow diet. Plasma lipoprotein profiling by FPLC in transgenic animals showed a higher peak in large-particle fractions corresponding to very low-density lipoprotein/chylomicrons when triglyceride content in the fractions was assayed. There was not much difference in cholesterol content in FPLC fractions, although a large low-density lipoprotein peak was identified in both nontransgenic and transgenic animals, resembling that found in humans. Further analysis revealed markedly delayed clearance of plasma triglyceride, accompanied by significantly reduced lipoprotein lipase activity in post-heparin plasma, in transgenic pigs as compared with nontransgenic controls. In summary, we have successfully generated a novel hypertriglyceridemic ApoCIII transgenic miniature pig model that could be of great value for studies on hyperlipidemia in relation to atherosclerotic disorders. We generated transgenic miniature swine expressing human ApoCIII through the transfection of somatic cells combined with nuclear transfer. Human ApoCIII expression was detected in the liver and intestine in transgenic pigs. These animals also exhibited increased plasma triglyceride and delayed clearance. This model could be of great value for studies on hypertriglyceridemia in relation with atherosclerosis.</description><identifier>ISSN: 1742-464X</identifier><identifier>EISSN: 1742-4658</identifier><identifier>DOI: 10.1111/j.1742-4658.2011.08401.x</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing Ltd</publisher><subject>Hogs ; Proteins ; Transgenic animals</subject><ispartof>The FEBS journal, 2012-01, Vol.279 (1), p.91-99</ispartof><rights>2011 The Authors Journal compilation © 2011 FEBS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Wei, Jingyuan</creatorcontrib><creatorcontrib>Ouyang, Hongsheng</creatorcontrib><creatorcontrib>Wang, Yuhui</creatorcontrib><creatorcontrib>Pang, Daxin</creatorcontrib><creatorcontrib>Cong, Nathan X</creatorcontrib><creatorcontrib>Wang, Tiedong</creatorcontrib><creatorcontrib>Leng, Bingfeng</creatorcontrib><creatorcontrib>Li, Dong</creatorcontrib><creatorcontrib>Li, Xiaoping</creatorcontrib><creatorcontrib>Wu, Rong</creatorcontrib><creatorcontrib>Ding, Yu</creatorcontrib><creatorcontrib>Gao, Fei</creatorcontrib><creatorcontrib>Deng, Yanhong</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Li, Ziyi</creatorcontrib><creatorcontrib>Lai, Liangxue</creatorcontrib><creatorcontrib>Feng, Haihua</creatorcontrib><creatorcontrib>Liu, George</creatorcontrib><creatorcontrib>Deng, Xuming</creatorcontrib><title>Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoproteinCIII</title><title>The FEBS journal</title><description>Hypertriglyceridemia has recently been considered to be an independent risk factor for coronary heart disease, in which apolipoprotein (Apo)CIII is one of the major contributory factors, as it is strongly correlated with plasma triglyceride levels. Although ApoCIII transgenic mice have been generated as an animal model for the study of hypertriglyceridemia, the features of lipoprotein metabolism in mice differ greatly from those in humans. Because of the great similarity between pigs and humans with respect to lipid metabolism and cardiovascular physiology, we generated transgenic miniature pigs expressing human ApoCIII by the transfection of somatic cells combined with nuclear transfer. The expression of human ApoCIII was detected in the liver and intestine of the transgenic pigs. As compared with nontransgenic controls, transgenic pigs showed significantly increased plasma triglyceride levels (83±36 versus 38±4mg·dL-1, P <0.01) when fed a chow diet. Plasma lipoprotein profiling by FPLC in transgenic animals showed a higher peak in large-particle fractions corresponding to very low-density lipoprotein/chylomicrons when triglyceride content in the fractions was assayed. There was not much difference in cholesterol content in FPLC fractions, although a large low-density lipoprotein peak was identified in both nontransgenic and transgenic animals, resembling that found in humans. Further analysis revealed markedly delayed clearance of plasma triglyceride, accompanied by significantly reduced lipoprotein lipase activity in post-heparin plasma, in transgenic pigs as compared with nontransgenic controls. In summary, we have successfully generated a novel hypertriglyceridemic ApoCIII transgenic miniature pig model that could be of great value for studies on hyperlipidemia in relation to atherosclerotic disorders. We generated transgenic miniature swine expressing human ApoCIII through the transfection of somatic cells combined with nuclear transfer. Human ApoCIII expression was detected in the liver and intestine in transgenic pigs. These animals also exhibited increased plasma triglyceride and delayed clearance. This model could be of great value for studies on hypertriglyceridemia in relation with atherosclerosis.</description><subject>Hogs</subject><subject>Proteins</subject><subject>Transgenic animals</subject><issn>1742-464X</issn><issn>1742-4658</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNpdjktLxDAUhYMoOI7-h-DKTetNkz6ylOKjMOBmFu6GNHPbydAmNUlhxl9vQXHh2dwD5-OeQwhlkLJFj8eUlSJLRJFXaQaMpVAJYOnpgqz-gss_Lz6uyU0IRwCeCylXZKwPyisd0ZsvFY2z1HVU0cN5Qh-96YezXqI9jkbT6JUNPdrFjsYaFWePdDI9Hd0eB4qnyWMIxvb0MI_KUjW5wUxu8i6isXXTNLfkqlNDwLvfuybbl-dt_ZZs3l-b-mmTTAXIhLdSC162AFIr1IWGLC_3wDTIjldSVaIoc1l1TIhOdp3ADIu8LbMWW-BQKr4mDz9vl-rPGUPcjSZoHAZl0c1hx7iUckFBLuj9P_ToZm-XcTvJoAIQkvFvFqRscA</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>Wei, Jingyuan</creator><creator>Ouyang, Hongsheng</creator><creator>Wang, Yuhui</creator><creator>Pang, Daxin</creator><creator>Cong, Nathan X</creator><creator>Wang, Tiedong</creator><creator>Leng, Bingfeng</creator><creator>Li, Dong</creator><creator>Li, Xiaoping</creator><creator>Wu, Rong</creator><creator>Ding, Yu</creator><creator>Gao, Fei</creator><creator>Deng, Yanhong</creator><creator>Liu, Bo</creator><creator>Li, Ziyi</creator><creator>Lai, Liangxue</creator><creator>Feng, Haihua</creator><creator>Liu, George</creator><creator>Deng, Xuming</creator><general>Blackwell Publishing Ltd</general><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope></search><sort><creationdate>20120101</creationdate><title>Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoproteinCIII</title><author>Wei, Jingyuan ; Ouyang, Hongsheng ; Wang, Yuhui ; Pang, Daxin ; Cong, Nathan X ; Wang, Tiedong ; Leng, Bingfeng ; Li, Dong ; Li, Xiaoping ; Wu, Rong ; Ding, Yu ; Gao, Fei ; Deng, Yanhong ; Liu, Bo ; Li, Ziyi ; Lai, Liangxue ; Feng, Haihua ; Liu, George ; Deng, Xuming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p609-3b9c437b009caec6c0257d01c09f389a8467598f144f9ff4e2e65b72beb0307a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Hogs</topic><topic>Proteins</topic><topic>Transgenic animals</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, Jingyuan</creatorcontrib><creatorcontrib>Ouyang, Hongsheng</creatorcontrib><creatorcontrib>Wang, Yuhui</creatorcontrib><creatorcontrib>Pang, Daxin</creatorcontrib><creatorcontrib>Cong, Nathan X</creatorcontrib><creatorcontrib>Wang, Tiedong</creatorcontrib><creatorcontrib>Leng, Bingfeng</creatorcontrib><creatorcontrib>Li, Dong</creatorcontrib><creatorcontrib>Li, Xiaoping</creatorcontrib><creatorcontrib>Wu, Rong</creatorcontrib><creatorcontrib>Ding, Yu</creatorcontrib><creatorcontrib>Gao, Fei</creatorcontrib><creatorcontrib>Deng, Yanhong</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Li, Ziyi</creatorcontrib><creatorcontrib>Lai, Liangxue</creatorcontrib><creatorcontrib>Feng, Haihua</creatorcontrib><creatorcontrib>Liu, George</creatorcontrib><creatorcontrib>Deng, Xuming</creatorcontrib><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><jtitle>The FEBS journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wei, Jingyuan</au><au>Ouyang, Hongsheng</au><au>Wang, Yuhui</au><au>Pang, Daxin</au><au>Cong, Nathan X</au><au>Wang, Tiedong</au><au>Leng, Bingfeng</au><au>Li, Dong</au><au>Li, Xiaoping</au><au>Wu, Rong</au><au>Ding, Yu</au><au>Gao, Fei</au><au>Deng, Yanhong</au><au>Liu, Bo</au><au>Li, Ziyi</au><au>Lai, Liangxue</au><au>Feng, Haihua</au><au>Liu, George</au><au>Deng, Xuming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoproteinCIII</atitle><jtitle>The FEBS journal</jtitle><date>2012-01-01</date><risdate>2012</risdate><volume>279</volume><issue>1</issue><spage>91</spage><epage>99</epage><pages>91-99</pages><issn>1742-464X</issn><eissn>1742-4658</eissn><abstract>Hypertriglyceridemia has recently been considered to be an independent risk factor for coronary heart disease, in which apolipoprotein (Apo)CIII is one of the major contributory factors, as it is strongly correlated with plasma triglyceride levels. Although ApoCIII transgenic mice have been generated as an animal model for the study of hypertriglyceridemia, the features of lipoprotein metabolism in mice differ greatly from those in humans. Because of the great similarity between pigs and humans with respect to lipid metabolism and cardiovascular physiology, we generated transgenic miniature pigs expressing human ApoCIII by the transfection of somatic cells combined with nuclear transfer. The expression of human ApoCIII was detected in the liver and intestine of the transgenic pigs. As compared with nontransgenic controls, transgenic pigs showed significantly increased plasma triglyceride levels (83±36 versus 38±4mg·dL-1, P <0.01) when fed a chow diet. Plasma lipoprotein profiling by FPLC in transgenic animals showed a higher peak in large-particle fractions corresponding to very low-density lipoprotein/chylomicrons when triglyceride content in the fractions was assayed. There was not much difference in cholesterol content in FPLC fractions, although a large low-density lipoprotein peak was identified in both nontransgenic and transgenic animals, resembling that found in humans. Further analysis revealed markedly delayed clearance of plasma triglyceride, accompanied by significantly reduced lipoprotein lipase activity in post-heparin plasma, in transgenic pigs as compared with nontransgenic controls. In summary, we have successfully generated a novel hypertriglyceridemic ApoCIII transgenic miniature pig model that could be of great value for studies on hyperlipidemia in relation to atherosclerotic disorders. We generated transgenic miniature swine expressing human ApoCIII through the transfection of somatic cells combined with nuclear transfer. Human ApoCIII expression was detected in the liver and intestine in transgenic pigs. These animals also exhibited increased plasma triglyceride and delayed clearance. This model could be of great value for studies on hypertriglyceridemia in relation with atherosclerosis.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><doi>10.1111/j.1742-4658.2011.08401.x</doi><tpages>9</tpages></addata></record> |
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| title | Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoproteinCIII |
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