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Characterization of immunoglobulin heavy chain knockout rats
The rat is a species frequently used in immunological studies but, until now, there were no models with introduced gene-specific mutations. In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we comp...
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Published in: | European journal of immunology 2010-10, Vol.40 (10), p.2932-2941 |
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creator | Ménoret, Séverine Iscache, Anne-L Tesson, Laurent Rémy, Séverine Usal, Claire Osborn, Michel J Cost, Gregory J Brüggemann, Marianne Buelow, Roland Anegon, Ignacio |
description | The rat is a species frequently used in immunological studies but, until now, there were no models with introduced gene-specific mutations. In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we compare immune development in two Ig heavy-chain KO lines; one with truncated Cμ and a new line with removed JH segments. Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH-deletion rats showed undetectable mRNA for all H-chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B-cell numbers were reduced >95% versus WT animals. In rats homozygous for IgM mutation, no Ab-mediated hyperacute allograft rejection was encountered. Similarities in B-cell differentiation seen in Ig KO rats and ES cell-derived Ig KO mice are discussed. These Ig and B-cell-deficient rats obtained using zinc-finger nucleases-technology should be useful as biomedical research models and a powerful platform for transgenic animals expressing a human Ab repertoire. |
doi_str_mv | 10.1002/eji.201040939 |
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In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we compare immune development in two Ig heavy-chain KO lines; one with truncated Cμ and a new line with removed JH segments. Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH-deletion rats showed undetectable mRNA for all H-chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B-cell numbers were reduced >95% versus WT animals. In rats homozygous for IgM mutation, no Ab-mediated hyperacute allograft rejection was encountered. Similarities in B-cell differentiation seen in Ig KO rats and ES cell-derived Ig KO mice are discussed. These Ig and B-cell-deficient rats obtained using zinc-finger nucleases-technology should be useful as biomedical research models and a powerful platform for transgenic animals expressing a human Ab repertoire.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.201040939</identifier><identifier>PMID: 21038471</identifier><identifier>CODEN: EJIMAF</identifier><language>eng</language><publisher>Weinheim: Wiley-VCH Verlag</publisher><subject>Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; B-Lymphocytes - cytology ; B-Lymphocytes - immunology ; B‐cell deficient ; Cell Differentiation - immunology ; Embryonic Stem Cells - immunology ; Graft Survival - immunology ; Heart Transplantation - immunology ; Immunoglobulin Constant Regions - genetics ; Immunoglobulin Constant Regions - immunology ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Heavy Chains - immunology ; Immunoglobulin Isotypes - blood ; Immunoglobulin Joining Region - genetics ; Immunoglobulin Joining Region - immunology ; Knockout rat ; Lymphoid Tissue - immunology ; Molecular Sequence Data ; Rats ; Rats, Inbred Lew ; Rats, Mutant Strains ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - chemistry ; RNA - genetics ; Specific Pathogen-Free Organisms ; Transgenic rat ; Zinc Fingers - genetics ; Zinc‐finger nucleases</subject><ispartof>European journal of immunology, 2010-10, Vol.40 (10), p.2932-2941</ispartof><rights>Copyright © 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4919-4ab73fc97de99e3d71fef6479a5b73153c75fdf89e41cc68d12c88a029b7b4e03</citedby><cites>FETCH-LOGICAL-c4919-4ab73fc97de99e3d71fef6479a5b73153c75fdf89e41cc68d12c88a029b7b4e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21038471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ménoret, Séverine</creatorcontrib><creatorcontrib>Iscache, Anne-L</creatorcontrib><creatorcontrib>Tesson, Laurent</creatorcontrib><creatorcontrib>Rémy, Séverine</creatorcontrib><creatorcontrib>Usal, Claire</creatorcontrib><creatorcontrib>Osborn, Michel J</creatorcontrib><creatorcontrib>Cost, Gregory J</creatorcontrib><creatorcontrib>Brüggemann, Marianne</creatorcontrib><creatorcontrib>Buelow, Roland</creatorcontrib><creatorcontrib>Anegon, Ignacio</creatorcontrib><title>Characterization of immunoglobulin heavy chain knockout rats</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>The rat is a species frequently used in immunological studies but, until now, there were no models with introduced gene-specific mutations. In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we compare immune development in two Ig heavy-chain KO lines; one with truncated Cμ and a new line with removed JH segments. Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH-deletion rats showed undetectable mRNA for all H-chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B-cell numbers were reduced >95% versus WT animals. In rats homozygous for IgM mutation, no Ab-mediated hyperacute allograft rejection was encountered. Similarities in B-cell differentiation seen in Ig KO rats and ES cell-derived Ig KO mice are discussed. These Ig and B-cell-deficient rats obtained using zinc-finger nucleases-technology should be useful as biomedical research models and a powerful platform for transgenic animals expressing a human Ab repertoire.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>B-Lymphocytes - cytology</subject><subject>B-Lymphocytes - immunology</subject><subject>B‐cell deficient</subject><subject>Cell Differentiation - immunology</subject><subject>Embryonic Stem Cells - immunology</subject><subject>Graft Survival - immunology</subject><subject>Heart Transplantation - immunology</subject><subject>Immunoglobulin Constant Regions - genetics</subject><subject>Immunoglobulin Constant Regions - immunology</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Heavy Chains - immunology</subject><subject>Immunoglobulin Isotypes - blood</subject><subject>Immunoglobulin Joining Region - genetics</subject><subject>Immunoglobulin Joining Region - immunology</subject><subject>Knockout rat</subject><subject>Lymphoid Tissue - immunology</subject><subject>Molecular Sequence Data</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Rats, Mutant Strains</subject><subject>Rats, Sprague-Dawley</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - chemistry</subject><subject>RNA - genetics</subject><subject>Specific Pathogen-Free Organisms</subject><subject>Transgenic rat</subject><subject>Zinc Fingers - genetics</subject><subject>Zinc‐finger nucleases</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp90cFvFCEUBnBiNHZbPXrVSTzUy9T3gIEh8WI21bZp0oP2TBgGumxnhgozmvWvF7NtYzz0BMn78QX4CHmDcIIA9KPbhhMKCBwUU8_IChuKNUeOz8kKAHlNVQsH5DDnLQAo0aiX5IAisJZLXJFP641Jxs4uhd9mDnGqoq_COC5TvBlitwxhqjbO_NxVdmPK_naK9jYuc5XMnF-RF94M2b2-X4_I9ZfT7-uz-vLq6_n682VtuUJVc9NJ5q2SvVPKsV6id15wqUxTBtgwKxvf-1Y5jtaKtkdq29YAVZ3suAN2RI73uXcp_lhcnvUYsnXDYCYXl6yloEARuSjyw5MSpRSCc2RNoe__o9u4pKm8oygh2nIv5EXVe2VTzDk5r-9SGE3aaQT9twBdCtCPBRT_9j516UbXP-qHHy9A7sGvMLjd02n69OL83-h3-5PeRG1uUsj6-lsZM8BWMaSM_QEeOpjl</recordid><startdate>201010</startdate><enddate>201010</enddate><creator>Ménoret, Séverine</creator><creator>Iscache, Anne-L</creator><creator>Tesson, Laurent</creator><creator>Rémy, Séverine</creator><creator>Usal, Claire</creator><creator>Osborn, Michel J</creator><creator>Cost, Gregory J</creator><creator>Brüggemann, Marianne</creator><creator>Buelow, Roland</creator><creator>Anegon, Ignacio</creator><general>Wiley-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley Subscription Services, Inc</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201010</creationdate><title>Characterization of immunoglobulin heavy chain knockout rats</title><author>Ménoret, Séverine ; 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In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we compare immune development in two Ig heavy-chain KO lines; one with truncated Cμ and a new line with removed JH segments. Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH-deletion rats showed undetectable mRNA for all H-chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B-cell numbers were reduced >95% versus WT animals. In rats homozygous for IgM mutation, no Ab-mediated hyperacute allograft rejection was encountered. Similarities in B-cell differentiation seen in Ig KO rats and ES cell-derived Ig KO mice are discussed. These Ig and B-cell-deficient rats obtained using zinc-finger nucleases-technology should be useful as biomedical research models and a powerful platform for transgenic animals expressing a human Ab repertoire.</abstract><cop>Weinheim</cop><pub>Wiley-VCH Verlag</pub><pmid>21038471</pmid><doi>10.1002/eji.201040939</doi><tpages>10</tpages></addata></record> |
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subjects | Amino Acid Sequence Animals Animals, Genetically Modified B-Lymphocytes - cytology B-Lymphocytes - immunology B‐cell deficient Cell Differentiation - immunology Embryonic Stem Cells - immunology Graft Survival - immunology Heart Transplantation - immunology Immunoglobulin Constant Regions - genetics Immunoglobulin Constant Regions - immunology Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Isotypes - blood Immunoglobulin Joining Region - genetics Immunoglobulin Joining Region - immunology Knockout rat Lymphoid Tissue - immunology Molecular Sequence Data Rats Rats, Inbred Lew Rats, Mutant Strains Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction RNA - chemistry RNA - genetics Specific Pathogen-Free Organisms Transgenic rat Zinc Fingers - genetics Zinc‐finger nucleases |
title | Characterization of immunoglobulin heavy chain knockout rats |
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