Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat
The risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study we show the involvement of SHR genetic variation that affects antibody formation and function in the pathogenesis of stroke. We h...
Gespeichert in:
| Veröffentlicht in: | Physiological genomics 2019-11, Vol.51 (11), p.578-585 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 585 |
|---|---|
| container_issue | 11 |
| container_start_page | 578 |
| container_title | Physiological genomics |
| container_volume | 51 |
| creator | Dhande, Isha S Kneedler, Sterling C Joshi, Aniket S Zhu, Yaming Hicks, M John Wenderfer, Scott E Braun, Michael C Doris, Peter A |
| description | The risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study we show the involvement of SHR genetic variation that affects antibody formation and function in the pathogenesis of stroke. We have tested the involvement in susceptibility to stroke of genetic variation in
, the gene encoding the immunoglobulin heavy chain by congenic substitution. This gene contains functional natural variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which the
gene was substituted with the corresponding haplotype from SHR-B2. Compared with SHR-A3 rats, congenic substitution of the
locus [SHR-A3(
-B2)] markedly reduced cerebrovascular disease. Given the role in antibody formation of the
gene, we investigated the presence of IgG and IgM autoantibodies and their targets using a high-density protein array containing ~20,000 recombinant proteins. High titers of autoantibodies to key cerebrovascular stress proteins were detected, including FABP4, HSP70, and Wnt signaling proteins. Serum levels of these autoantibodies were reduced in the SHR-A3(
-B2) congenic line. |
| doi_str_mv | 10.1152/physiolgenomics.00054.2019 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6879812</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2314264247</sourcerecordid><originalsourceid>FETCH-LOGICAL-c454t-edeaaa521c8fb5156703fb3bcb825ea197b26360997e3b0661bf8e68fda0e84f3</originalsourceid><addsrcrecordid>eNpdkU1rFTEUhgdRbK3-BQm6cTM135NxIZSiVSi40XVIcs_cSZ1JxiRzYZb-c1NvW7SrHMhzXs7L0zRvCD4nRND3y7hlH6c9hDh7l88xxoKfU0z6J80pEYy0lMruaZ1xz1vFODlpXuR8gzHhnRLPmxNGJFad6k-b31eQ5nbyAVDNg-IdOpjkTfExIB9QGQH5eV5D3E_RrhVEI5jDhtxo6uwSmAIZ5ZLiT0B5zQ6W4q2ffNnu9_MSQzEB4pqnDY3bAqlAyP4AKJnysnk2mCnDq7v3rPnx-dP3yy_t9berr5cX163jgpcWdmCMEZQ4NVhBhOwwGyyzzioqwJC-s1Qyifu-A2axlMQOCqQadgaD4gM7az4ec5fVzrBzEEoyk16Sn03adDRe__8T_Kj38aCl6npFaA14dxeQ4q8VctGzr3Wn6VhNU1Y1dKLrRUXfPkJv4ppCrVcpwqnklHeV-nCkXIo5JxgejiFY35rWj0zrv6b1rem6_PrfOg-r92rZHwYVr38</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2314264247</pqid></control><display><type>article</type><title>Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat</title><source>American Physiological Society</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Dhande, Isha S ; Kneedler, Sterling C ; Joshi, Aniket S ; Zhu, Yaming ; Hicks, M John ; Wenderfer, Scott E ; Braun, Michael C ; Doris, Peter A</creator><creatorcontrib>Dhande, Isha S ; Kneedler, Sterling C ; Joshi, Aniket S ; Zhu, Yaming ; Hicks, M John ; Wenderfer, Scott E ; Braun, Michael C ; Doris, Peter A</creatorcontrib><description>The risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study we show the involvement of SHR genetic variation that affects antibody formation and function in the pathogenesis of stroke. We have tested the involvement in susceptibility to stroke of genetic variation in
, the gene encoding the immunoglobulin heavy chain by congenic substitution. This gene contains functional natural variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which the
gene was substituted with the corresponding haplotype from SHR-B2. Compared with SHR-A3 rats, congenic substitution of the
locus [SHR-A3(
-B2)] markedly reduced cerebrovascular disease. Given the role in antibody formation of the
gene, we investigated the presence of IgG and IgM autoantibodies and their targets using a high-density protein array containing ~20,000 recombinant proteins. High titers of autoantibodies to key cerebrovascular stress proteins were detected, including FABP4, HSP70, and Wnt signaling proteins. Serum levels of these autoantibodies were reduced in the SHR-A3(
-B2) congenic line.</description><identifier>ISSN: 1094-8341</identifier><identifier>EISSN: 1531-2267</identifier><identifier>DOI: 10.1152/physiolgenomics.00054.2019</identifier><identifier>PMID: 31608789</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Autoantibodies ; Cerebrovascular diseases ; Genetic diversity ; Heavy chains ; Hsp70 protein ; Hypertension ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Protein arrays ; Proteins ; Rodents ; Serum levels ; Stress proteins ; Wnt protein</subject><ispartof>Physiological genomics, 2019-11, Vol.51 (11), p.578-585</ispartof><rights>Copyright American Physiological Society Nov 2019</rights><rights>Copyright © 2019 the American Physiological Society 2019 American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-edeaaa521c8fb5156703fb3bcb825ea197b26360997e3b0661bf8e68fda0e84f3</citedby><cites>FETCH-LOGICAL-c454t-edeaaa521c8fb5156703fb3bcb825ea197b26360997e3b0661bf8e68fda0e84f3</cites><orcidid>0000-0002-8991-8277</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31608789$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dhande, Isha S</creatorcontrib><creatorcontrib>Kneedler, Sterling C</creatorcontrib><creatorcontrib>Joshi, Aniket S</creatorcontrib><creatorcontrib>Zhu, Yaming</creatorcontrib><creatorcontrib>Hicks, M John</creatorcontrib><creatorcontrib>Wenderfer, Scott E</creatorcontrib><creatorcontrib>Braun, Michael C</creatorcontrib><creatorcontrib>Doris, Peter A</creatorcontrib><title>Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat</title><title>Physiological genomics</title><addtitle>Physiol Genomics</addtitle><description>The risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study we show the involvement of SHR genetic variation that affects antibody formation and function in the pathogenesis of stroke. We have tested the involvement in susceptibility to stroke of genetic variation in
, the gene encoding the immunoglobulin heavy chain by congenic substitution. This gene contains functional natural variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which the
gene was substituted with the corresponding haplotype from SHR-B2. Compared with SHR-A3 rats, congenic substitution of the
locus [SHR-A3(
-B2)] markedly reduced cerebrovascular disease. Given the role in antibody formation of the
gene, we investigated the presence of IgG and IgM autoantibodies and their targets using a high-density protein array containing ~20,000 recombinant proteins. High titers of autoantibodies to key cerebrovascular stress proteins were detected, including FABP4, HSP70, and Wnt signaling proteins. Serum levels of these autoantibodies were reduced in the SHR-A3(
-B2) congenic line.</description><subject>Autoantibodies</subject><subject>Cerebrovascular diseases</subject><subject>Genetic diversity</subject><subject>Heavy chains</subject><subject>Hsp70 protein</subject><subject>Hypertension</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulins</subject><subject>Protein arrays</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Serum levels</subject><subject>Stress proteins</subject><subject>Wnt protein</subject><issn>1094-8341</issn><issn>1531-2267</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkU1rFTEUhgdRbK3-BQm6cTM135NxIZSiVSi40XVIcs_cSZ1JxiRzYZb-c1NvW7SrHMhzXs7L0zRvCD4nRND3y7hlH6c9hDh7l88xxoKfU0z6J80pEYy0lMruaZ1xz1vFODlpXuR8gzHhnRLPmxNGJFad6k-b31eQ5nbyAVDNg-IdOpjkTfExIB9QGQH5eV5D3E_RrhVEI5jDhtxo6uwSmAIZ5ZLiT0B5zQ6W4q2ffNnu9_MSQzEB4pqnDY3bAqlAyP4AKJnysnk2mCnDq7v3rPnx-dP3yy_t9berr5cX163jgpcWdmCMEZQ4NVhBhOwwGyyzzioqwJC-s1Qyifu-A2axlMQOCqQadgaD4gM7az4ec5fVzrBzEEoyk16Sn03adDRe__8T_Kj38aCl6npFaA14dxeQ4q8VctGzr3Wn6VhNU1Y1dKLrRUXfPkJv4ppCrVcpwqnklHeV-nCkXIo5JxgejiFY35rWj0zrv6b1rem6_PrfOg-r92rZHwYVr38</recordid><startdate>20191101</startdate><enddate>20191101</enddate><creator>Dhande, Isha S</creator><creator>Kneedler, Sterling C</creator><creator>Joshi, Aniket S</creator><creator>Zhu, Yaming</creator><creator>Hicks, M John</creator><creator>Wenderfer, Scott E</creator><creator>Braun, Michael C</creator><creator>Doris, Peter A</creator><general>American Physiological Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8991-8277</orcidid></search><sort><creationdate>20191101</creationdate><title>Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat</title><author>Dhande, Isha S ; Kneedler, Sterling C ; Joshi, Aniket S ; Zhu, Yaming ; Hicks, M John ; Wenderfer, Scott E ; Braun, Michael C ; Doris, Peter A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-edeaaa521c8fb5156703fb3bcb825ea197b26360997e3b0661bf8e68fda0e84f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Autoantibodies</topic><topic>Cerebrovascular diseases</topic><topic>Genetic diversity</topic><topic>Heavy chains</topic><topic>Hsp70 protein</topic><topic>Hypertension</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin M</topic><topic>Immunoglobulins</topic><topic>Protein arrays</topic><topic>Proteins</topic><topic>Rodents</topic><topic>Serum levels</topic><topic>Stress proteins</topic><topic>Wnt protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dhande, Isha S</creatorcontrib><creatorcontrib>Kneedler, Sterling C</creatorcontrib><creatorcontrib>Joshi, Aniket S</creatorcontrib><creatorcontrib>Zhu, Yaming</creatorcontrib><creatorcontrib>Hicks, M John</creatorcontrib><creatorcontrib>Wenderfer, Scott E</creatorcontrib><creatorcontrib>Braun, Michael C</creatorcontrib><creatorcontrib>Doris, Peter A</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Physiological genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dhande, Isha S</au><au>Kneedler, Sterling C</au><au>Joshi, Aniket S</au><au>Zhu, Yaming</au><au>Hicks, M John</au><au>Wenderfer, Scott E</au><au>Braun, Michael C</au><au>Doris, Peter A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat</atitle><jtitle>Physiological genomics</jtitle><addtitle>Physiol Genomics</addtitle><date>2019-11-01</date><risdate>2019</risdate><volume>51</volume><issue>11</issue><spage>578</spage><epage>585</epage><pages>578-585</pages><issn>1094-8341</issn><eissn>1531-2267</eissn><abstract>The risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study we show the involvement of SHR genetic variation that affects antibody formation and function in the pathogenesis of stroke. We have tested the involvement in susceptibility to stroke of genetic variation in
, the gene encoding the immunoglobulin heavy chain by congenic substitution. This gene contains functional natural variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which the
gene was substituted with the corresponding haplotype from SHR-B2. Compared with SHR-A3 rats, congenic substitution of the
locus [SHR-A3(
-B2)] markedly reduced cerebrovascular disease. Given the role in antibody formation of the
gene, we investigated the presence of IgG and IgM autoantibodies and their targets using a high-density protein array containing ~20,000 recombinant proteins. High titers of autoantibodies to key cerebrovascular stress proteins were detected, including FABP4, HSP70, and Wnt signaling proteins. Serum levels of these autoantibodies were reduced in the SHR-A3(
-B2) congenic line.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>31608789</pmid><doi>10.1152/physiolgenomics.00054.2019</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-8991-8277</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1094-8341 |
| ispartof | Physiological genomics, 2019-11, Vol.51 (11), p.578-585 |
| issn | 1094-8341 1531-2267 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6879812 |
| source | American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Autoantibodies Cerebrovascular diseases Genetic diversity Heavy chains Hsp70 protein Hypertension Immunoglobulin G Immunoglobulin M Immunoglobulins Protein arrays Proteins Rodents Serum levels Stress proteins Wnt protein |
| title | Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T21%3A58%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Germ-line%20genetic%20variation%20in%20the%20immunoglobulin%20heavy%20chain%20creates%20stroke%20susceptibility%20in%20the%20spontaneously%20hypertensive%20rat&rft.jtitle=Physiological%20genomics&rft.au=Dhande,%20Isha%20S&rft.date=2019-11-01&rft.volume=51&rft.issue=11&rft.spage=578&rft.epage=585&rft.pages=578-585&rft.issn=1094-8341&rft.eissn=1531-2267&rft_id=info:doi/10.1152/physiolgenomics.00054.2019&rft_dat=%3Cproquest_pubme%3E2314264247%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2314264247&rft_id=info:pmid/31608789&rfr_iscdi=true |