Transgenic expression of a CD46 (membrane cofactor protein) minigene: Studies of xenotransplantation and measles virus infection
CD46 (membrane cofactor protein) is a human cell‐surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement act...
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| Veröffentlicht in: | European journal of immunology 1997-03, Vol.27 (3), p.726-734 |
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| container_title | European journal of immunology |
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| creator | Thorley, Bruce R. Milland, Julie Christiansen, Dale Lanteri, Marc B. McInnes, Beth Moeller, Ingrid Rivailler, Pierre Horvat, Branka Rabourdin‐Combe, Chantal Gerlier, Denis McKenzie, Ian F. C. Loveland, Bruc. E. E. |
| description | CD46 (membrane cofactor protein) is a human cell‐surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement activation by complement regulators in hyperacute rejection of xenografts, and (ii) measles virus infection. The mouse line was made using a CD46 minigene that includes promoter sequence and the first two introns of genomic CD46, which was coinjected into mouse ova with chicken lysozyme matrix attachment region DNA. A high level of CD46 expression in homozygotic transgenic mice was obtained with spleen cells having approximately 75% of the level found on human peripheral blood mononuclear cells. CD46 was detected in all tissues examined by immunohistochemistry, radioimmunoassay and Western blotting, showing that these mice were suitable for transplantation and measles virus infection studies. It also indicated that the transgene included the important regulatory elements of the CD46 promoter. Transgenic spleen cells were significantly protected in vitro from human complement activated by either the classical or alternative pathways and from alternative pathway rat complement. Furthermore, transgenic mouse hearts transplanted to rats regulated complement deposition in an in vivo model of antibody‐dependent hyperacute xenograft rejection. Similar to human lymphocytes, transgenic lymphoblasts could be infected in vitro with measles virus; infected cells expressed viral proteins and produced infectious viral particles. The data demonstrate the suitability of this minigene for obtaining high‐level CD46 expression sufficient for enhanced resistance of transgenic cells to complement attack and for obtaining wide tissue distribution of CD46, analogous to human tissues and, therefore, useful for comparative studies. |
| doi_str_mv | 10.1002/eji.1830270322 |
| format | Article |
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C. ; Loveland, Bruc. E. E.</creator><creatorcontrib>Thorley, Bruce R. ; Milland, Julie ; Christiansen, Dale ; Lanteri, Marc B. ; McInnes, Beth ; Moeller, Ingrid ; Rivailler, Pierre ; Horvat, Branka ; Rabourdin‐Combe, Chantal ; Gerlier, Denis ; McKenzie, Ian F. C. ; Loveland, Bruc. E. E.</creatorcontrib><description>CD46 (membrane cofactor protein) is a human cell‐surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement activation by complement regulators in hyperacute rejection of xenografts, and (ii) measles virus infection. The mouse line was made using a CD46 minigene that includes promoter sequence and the first two introns of genomic CD46, which was coinjected into mouse ova with chicken lysozyme matrix attachment region DNA. A high level of CD46 expression in homozygotic transgenic mice was obtained with spleen cells having approximately 75% of the level found on human peripheral blood mononuclear cells. CD46 was detected in all tissues examined by immunohistochemistry, radioimmunoassay and Western blotting, showing that these mice were suitable for transplantation and measles virus infection studies. It also indicated that the transgene included the important regulatory elements of the CD46 promoter. Transgenic spleen cells were significantly protected in vitro from human complement activated by either the classical or alternative pathways and from alternative pathway rat complement. Furthermore, transgenic mouse hearts transplanted to rats regulated complement deposition in an in vivo model of antibody‐dependent hyperacute xenograft rejection. Similar to human lymphocytes, transgenic lymphoblasts could be infected in vitro with measles virus; infected cells expressed viral proteins and produced infectious viral particles. The data demonstrate the suitability of this minigene for obtaining high‐level CD46 expression sufficient for enhanced resistance of transgenic cells to complement attack and for obtaining wide tissue distribution of CD46, analogous to human tissues and, therefore, useful for comparative studies.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.1830270322</identifier><identifier>PMID: 9079815</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag GmbH</publisher><subject>Acute Disease ; Animals ; Antigens, CD - physiology ; Complement Pathway, Alternative ; Complement regulation ; Complement System Proteins - metabolism ; Graft Rejection - immunology ; Humans ; Life Sciences ; Measles - immunology ; Measles infection ; measles virus ; Measles virus - growth & development ; Measles virus - immunology ; Membrane Cofactor Protein ; Membrane Glycoproteins - physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Microbiology and Parasitology ; Minigene ; Rats ; Tissue Distribution ; Transgene expression ; Transplantation, Heterologous ; Virology ; Xenotransplantation</subject><ispartof>European journal of immunology, 1997-03, Vol.27 (3), p.726-734</ispartof><rights>Copyright © 1997 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4052-e18dd6293b2a1335ce1f96a3b18c5c0f0ca3204c785ebeea6bcacbbc979ef3143</citedby><cites>FETCH-LOGICAL-c4052-e18dd6293b2a1335ce1f96a3b18c5c0f0ca3204c785ebeea6bcacbbc979ef3143</cites><orcidid>0000-0003-0578-7765 ; 0000-0001-5539-456X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Feji.1830270322$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.1830270322$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9079815$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02475187$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Thorley, Bruce R.</creatorcontrib><creatorcontrib>Milland, Julie</creatorcontrib><creatorcontrib>Christiansen, Dale</creatorcontrib><creatorcontrib>Lanteri, Marc B.</creatorcontrib><creatorcontrib>McInnes, Beth</creatorcontrib><creatorcontrib>Moeller, Ingrid</creatorcontrib><creatorcontrib>Rivailler, Pierre</creatorcontrib><creatorcontrib>Horvat, Branka</creatorcontrib><creatorcontrib>Rabourdin‐Combe, Chantal</creatorcontrib><creatorcontrib>Gerlier, Denis</creatorcontrib><creatorcontrib>McKenzie, Ian F. C.</creatorcontrib><creatorcontrib>Loveland, Bruc. E. E.</creatorcontrib><title>Transgenic expression of a CD46 (membrane cofactor protein) minigene: Studies of xenotransplantation and measles virus infection</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>CD46 (membrane cofactor protein) is a human cell‐surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement activation by complement regulators in hyperacute rejection of xenografts, and (ii) measles virus infection. The mouse line was made using a CD46 minigene that includes promoter sequence and the first two introns of genomic CD46, which was coinjected into mouse ova with chicken lysozyme matrix attachment region DNA. A high level of CD46 expression in homozygotic transgenic mice was obtained with spleen cells having approximately 75% of the level found on human peripheral blood mononuclear cells. CD46 was detected in all tissues examined by immunohistochemistry, radioimmunoassay and Western blotting, showing that these mice were suitable for transplantation and measles virus infection studies. It also indicated that the transgene included the important regulatory elements of the CD46 promoter. Transgenic spleen cells were significantly protected in vitro from human complement activated by either the classical or alternative pathways and from alternative pathway rat complement. Furthermore, transgenic mouse hearts transplanted to rats regulated complement deposition in an in vivo model of antibody‐dependent hyperacute xenograft rejection. Similar to human lymphocytes, transgenic lymphoblasts could be infected in vitro with measles virus; infected cells expressed viral proteins and produced infectious viral particles. The data demonstrate the suitability of this minigene for obtaining high‐level CD46 expression sufficient for enhanced resistance of transgenic cells to complement attack and for obtaining wide tissue distribution of CD46, analogous to human tissues and, therefore, useful for comparative studies.</description><subject>Acute Disease</subject><subject>Animals</subject><subject>Antigens, CD - physiology</subject><subject>Complement Pathway, Alternative</subject><subject>Complement regulation</subject><subject>Complement System Proteins - metabolism</subject><subject>Graft Rejection - immunology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Measles - immunology</subject><subject>Measles infection</subject><subject>measles virus</subject><subject>Measles virus - growth & development</subject><subject>Measles virus - immunology</subject><subject>Membrane Cofactor Protein</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CBA</subject><subject>Microbiology and Parasitology</subject><subject>Minigene</subject><subject>Rats</subject><subject>Tissue Distribution</subject><subject>Transgene expression</subject><subject>Transplantation, Heterologous</subject><subject>Virology</subject><subject>Xenotransplantation</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1vFDEURS0ECkugpUNyhUgxm2d7Pmy6aBNI0EopCLXl8bwBRzP2Ys-EpMtPx6NdBbpUlvzOPfbTJeQ9gzUD4Kd469ZMCuANCM5fkBWrOCtKVrKXZAXAyoIrCa_Jm5RuAUDVlToiRwoaJVm1Io830fj0E72zFO93EVNywdPQU0M352VNP404tplBakNv7BQi3cUwofMndHTe5Sh-pt-nuXOYltw9-jAt0t1g_GSmRWd8R0c0acjInYtzos73aJfZW_KqN0PCd4fzmPz4cnGzuSy211-vNmfbwpZQ8QKZ7LqaK9Fyw4SoLLJe1Ua0TNrKQg_WCA6lbWSFLaKpW2ts21rVKOwFK8UxOdl7f5lB76IbTXzQwTh9ebbVyx3wsqmYbO5YZj_u2bzp7xnTpEeXLA55IQxz0o1UwKV4HmQ1iFI2y-vrPWhjSCli__QFBnrpUece9b8ec-DDwTy3I3ZP-KG4PFf7-R834MMzNn3x7eo_919KeqrX</recordid><startdate>199703</startdate><enddate>199703</enddate><creator>Thorley, Bruce R.</creator><creator>Milland, Julie</creator><creator>Christiansen, Dale</creator><creator>Lanteri, Marc B.</creator><creator>McInnes, Beth</creator><creator>Moeller, Ingrid</creator><creator>Rivailler, Pierre</creator><creator>Horvat, Branka</creator><creator>Rabourdin‐Combe, Chantal</creator><creator>Gerlier, Denis</creator><creator>McKenzie, Ian F. 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C.</au><au>Loveland, Bruc. E. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transgenic expression of a CD46 (membrane cofactor protein) minigene: Studies of xenotransplantation and measles virus infection</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>1997-03</date><risdate>1997</risdate><volume>27</volume><issue>3</issue><spage>726</spage><epage>734</epage><pages>726-734</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>CD46 (membrane cofactor protein) is a human cell‐surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement activation by complement regulators in hyperacute rejection of xenografts, and (ii) measles virus infection. The mouse line was made using a CD46 minigene that includes promoter sequence and the first two introns of genomic CD46, which was coinjected into mouse ova with chicken lysozyme matrix attachment region DNA. A high level of CD46 expression in homozygotic transgenic mice was obtained with spleen cells having approximately 75% of the level found on human peripheral blood mononuclear cells. CD46 was detected in all tissues examined by immunohistochemistry, radioimmunoassay and Western blotting, showing that these mice were suitable for transplantation and measles virus infection studies. It also indicated that the transgene included the important regulatory elements of the CD46 promoter. Transgenic spleen cells were significantly protected in vitro from human complement activated by either the classical or alternative pathways and from alternative pathway rat complement. Furthermore, transgenic mouse hearts transplanted to rats regulated complement deposition in an in vivo model of antibody‐dependent hyperacute xenograft rejection. Similar to human lymphocytes, transgenic lymphoblasts could be infected in vitro with measles virus; infected cells expressed viral proteins and produced infectious viral particles. The data demonstrate the suitability of this minigene for obtaining high‐level CD46 expression sufficient for enhanced resistance of transgenic cells to complement attack and for obtaining wide tissue distribution of CD46, analogous to human tissues and, therefore, useful for comparative studies.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag GmbH</pub><pmid>9079815</pmid><doi>10.1002/eji.1830270322</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0578-7765</orcidid><orcidid>https://orcid.org/0000-0001-5539-456X</orcidid></addata></record> |
| fulltext | fulltext |
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| ispartof | European journal of immunology, 1997-03, Vol.27 (3), p.726-734 |
| issn | 0014-2980 1521-4141 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Acute Disease Animals Antigens, CD - physiology Complement Pathway, Alternative Complement regulation Complement System Proteins - metabolism Graft Rejection - immunology Humans Life Sciences Measles - immunology Measles infection measles virus Measles virus - growth & development Measles virus - immunology Membrane Cofactor Protein Membrane Glycoproteins - physiology Mice Mice, Inbred C57BL Mice, Inbred CBA Microbiology and Parasitology Minigene Rats Tissue Distribution Transgene expression Transplantation, Heterologous Virology Xenotransplantation |
| title | Transgenic expression of a CD46 (membrane cofactor protein) minigene: Studies of xenotransplantation and measles virus infection |
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