Laboratory mice born to wild mice have natural microbiota and model human immune responses
Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creat...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2019-08, Vol.365 (6452), p.461-461 |
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| creator | Rosshart, Stephan P. Herz, Jasmin Vassallo, Brian G. Hunter, Ashli Wall, Morgan K. Badger, Jonathan H. McCulloch, John A. Anastasakis, Dimitrios G. Sarshad, Aishe A. Leonardi, Irina Collins, Nicholas Blatter, Joshua A. Han, Seong-Ji Tamoutounour, Samira Potapova, Svetlana St. Claire, Mark B. Foster Yuan, Wuxing Sen, Shurjo K. Dreier, Matthew S. Hild, Benedikt Hafner, Markus Wang, David Iliev, Iliyan D. Belkaid, Yasmine Trinchieri, Giorgio Rehermann, Barbara |
| description | Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creating "wildlings." These mice have a natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice. The bacterial microbiome, mycobiome, and virome of wildlings affect the immune landscape of multiple organs. Their gut microbiota outcompete laboratory microbiota and demonstrate resilience to environmental challenges. Wildlings, but not conventional laboratory mice, phenocopied human immune responses in two preclinical studies. A combined natural microbiota- and pathogen-based model may enhance the reproducibility of biomedical studies and increase the bench-to-bedside safety and success of immunological studies. |
| doi_str_mv | 10.1126/science.aaw4361 |
| format | Article |
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Foster ; Yuan, Wuxing ; Sen, Shurjo K. ; Dreier, Matthew S. ; Hild, Benedikt ; Hafner, Markus ; Wang, David ; Iliev, Iliyan D. ; Belkaid, Yasmine ; Trinchieri, Giorgio ; Rehermann, Barbara</creator><creatorcontrib>Rosshart, Stephan P. ; Herz, Jasmin ; Vassallo, Brian G. ; Hunter, Ashli ; Wall, Morgan K. ; Badger, Jonathan H. ; McCulloch, John A. ; Anastasakis, Dimitrios G. ; Sarshad, Aishe A. ; Leonardi, Irina ; Collins, Nicholas ; Blatter, Joshua A. ; Han, Seong-Ji ; Tamoutounour, Samira ; Potapova, Svetlana ; St. Claire, Mark B. Foster ; Yuan, Wuxing ; Sen, Shurjo K. ; Dreier, Matthew S. ; Hild, Benedikt ; Hafner, Markus ; Wang, David ; Iliev, Iliyan D. ; Belkaid, Yasmine ; Trinchieri, Giorgio ; Rehermann, Barbara</creatorcontrib><description>Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creating "wildlings." These mice have a natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice. The bacterial microbiome, mycobiome, and virome of wildlings affect the immune landscape of multiple organs. Their gut microbiota outcompete laboratory microbiota and demonstrate resilience to environmental challenges. Wildlings, but not conventional laboratory mice, phenocopied human immune responses in two preclinical studies. A combined natural microbiota- and pathogen-based model may enhance the reproducibility of biomedical studies and increase the bench-to-bedside safety and success of immunological studies.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aaw4361</identifier><identifier>PMID: 31371577</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Adaptive immunity ; Animal models ; Animals ; Animals, Wild - microbiology ; Antibiotics ; Bacteria ; Blood ; CD28 antigen ; Cell activation ; Clinical trials ; Cytokines ; Cytometry ; Diet ; Embryos ; Endotoxemia ; Environmental conditions ; Fc receptors ; Feedback (Response) ; Fusion protein ; Gastrointestinal Microbiome ; Gene sequencing ; Genetics ; Genomes ; Genotype & phenotype ; Host Microbial Interactions - immunology ; Host-Pathogen Interactions - immunology ; Human behavior ; Human response ; Humans ; Immune system ; Immunity ; Immunology ; Immunoregulation ; Inbreeding ; Inflammatory diseases ; Innate immunity ; Intestinal microflora ; Laboratories ; Lymphocytes ; Lymphocytes T ; Mammals ; Medical research ; Medical treatment ; Metabolism ; Mice ; Mice, Inbred C57BL ; Microbiota ; Microorganisms ; Models, Animal ; Neurodegenerative diseases ; Neurological diseases ; Organs ; Pathogens ; Phenotypes ; Physiology ; Reproducibility ; RESEARCH ARTICLE SUMMARY ; Research facilities ; Ribonucleic acid ; RNA ; Rodents ; Septic shock ; Skin ; Spleen ; Translation ; Translational Medical Research - standards ; Tumor necrosis factor-TNF ; Vagina</subject><ispartof>Science (American Association for the Advancement of Science), 2019-08, Vol.365 (6452), p.461-461</ispartof><rights>Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</rights><rights>Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-483f34498ba2f2bdbaa12bf24329ddc15c50876ed8263791c933b13b6fb8974d3</citedby><cites>FETCH-LOGICAL-c509t-483f34498ba2f2bdbaa12bf24329ddc15c50876ed8263791c933b13b6fb8974d3</cites><orcidid>0000-0001-6154-8924 ; 0000-0002-4336-6518 ; 0000-0002-0369-7371 ; 0000-0002-5781-721X ; 0000-0003-2645-664X ; 0000-0002-6989-8686 ; 0000-0001-5892-7464 ; 0000-0002-4948-1023 ; 0000-0002-5662-423X ; 0000-0001-9962-3571 ; 0000-0003-0884-9749 ; 0000-0001-6832-9951</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,2871,2872,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31371577$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rosshart, Stephan P.</creatorcontrib><creatorcontrib>Herz, Jasmin</creatorcontrib><creatorcontrib>Vassallo, Brian G.</creatorcontrib><creatorcontrib>Hunter, Ashli</creatorcontrib><creatorcontrib>Wall, Morgan K.</creatorcontrib><creatorcontrib>Badger, Jonathan H.</creatorcontrib><creatorcontrib>McCulloch, John A.</creatorcontrib><creatorcontrib>Anastasakis, Dimitrios G.</creatorcontrib><creatorcontrib>Sarshad, Aishe A.</creatorcontrib><creatorcontrib>Leonardi, Irina</creatorcontrib><creatorcontrib>Collins, Nicholas</creatorcontrib><creatorcontrib>Blatter, Joshua A.</creatorcontrib><creatorcontrib>Han, Seong-Ji</creatorcontrib><creatorcontrib>Tamoutounour, Samira</creatorcontrib><creatorcontrib>Potapova, Svetlana</creatorcontrib><creatorcontrib>St. Claire, Mark B. Foster</creatorcontrib><creatorcontrib>Yuan, Wuxing</creatorcontrib><creatorcontrib>Sen, Shurjo K.</creatorcontrib><creatorcontrib>Dreier, Matthew S.</creatorcontrib><creatorcontrib>Hild, Benedikt</creatorcontrib><creatorcontrib>Hafner, Markus</creatorcontrib><creatorcontrib>Wang, David</creatorcontrib><creatorcontrib>Iliev, Iliyan D.</creatorcontrib><creatorcontrib>Belkaid, Yasmine</creatorcontrib><creatorcontrib>Trinchieri, Giorgio</creatorcontrib><creatorcontrib>Rehermann, Barbara</creatorcontrib><title>Laboratory mice born to wild mice have natural microbiota and model human immune responses</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creating "wildlings." These mice have a natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice. The bacterial microbiome, mycobiome, and virome of wildlings affect the immune landscape of multiple organs. Their gut microbiota outcompete laboratory microbiota and demonstrate resilience to environmental challenges. Wildlings, but not conventional laboratory mice, phenocopied human immune responses in two preclinical studies. 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Foster ; Yuan, Wuxing ; Sen, Shurjo K. ; Dreier, Matthew S. ; Hild, Benedikt ; Hafner, Markus ; Wang, David ; Iliev, Iliyan D. ; Belkaid, Yasmine ; Trinchieri, Giorgio ; Rehermann, Barbara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-483f34498ba2f2bdbaa12bf24329ddc15c50876ed8263791c933b13b6fb8974d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adaptive immunity</topic><topic>Animal models</topic><topic>Animals</topic><topic>Animals, Wild - microbiology</topic><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Blood</topic><topic>CD28 antigen</topic><topic>Cell activation</topic><topic>Clinical trials</topic><topic>Cytokines</topic><topic>Cytometry</topic><topic>Diet</topic><topic>Embryos</topic><topic>Endotoxemia</topic><topic>Environmental conditions</topic><topic>Fc receptors</topic><topic>Feedback (Response)</topic><topic>Fusion protein</topic><topic>Gastrointestinal Microbiome</topic><topic>Gene sequencing</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Host Microbial Interactions - immunology</topic><topic>Host-Pathogen Interactions - immunology</topic><topic>Human behavior</topic><topic>Human response</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Immunology</topic><topic>Immunoregulation</topic><topic>Inbreeding</topic><topic>Inflammatory diseases</topic><topic>Innate immunity</topic><topic>Intestinal microflora</topic><topic>Laboratories</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mammals</topic><topic>Medical research</topic><topic>Medical treatment</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiota</topic><topic>Microorganisms</topic><topic>Models, Animal</topic><topic>Neurodegenerative diseases</topic><topic>Neurological diseases</topic><topic>Organs</topic><topic>Pathogens</topic><topic>Phenotypes</topic><topic>Physiology</topic><topic>Reproducibility</topic><topic>RESEARCH ARTICLE SUMMARY</topic><topic>Research facilities</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Rodents</topic><topic>Septic shock</topic><topic>Skin</topic><topic>Spleen</topic><topic>Translation</topic><topic>Translational Medical Research - standards</topic><topic>Tumor necrosis factor-TNF</topic><topic>Vagina</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rosshart, Stephan P.</creatorcontrib><creatorcontrib>Herz, Jasmin</creatorcontrib><creatorcontrib>Vassallo, Brian G.</creatorcontrib><creatorcontrib>Hunter, Ashli</creatorcontrib><creatorcontrib>Wall, Morgan K.</creatorcontrib><creatorcontrib>Badger, Jonathan H.</creatorcontrib><creatorcontrib>McCulloch, John A.</creatorcontrib><creatorcontrib>Anastasakis, Dimitrios G.</creatorcontrib><creatorcontrib>Sarshad, Aishe A.</creatorcontrib><creatorcontrib>Leonardi, Irina</creatorcontrib><creatorcontrib>Collins, Nicholas</creatorcontrib><creatorcontrib>Blatter, Joshua A.</creatorcontrib><creatorcontrib>Han, Seong-Ji</creatorcontrib><creatorcontrib>Tamoutounour, Samira</creatorcontrib><creatorcontrib>Potapova, Svetlana</creatorcontrib><creatorcontrib>St. Claire, Mark B. 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Foster</au><au>Yuan, Wuxing</au><au>Sen, Shurjo K.</au><au>Dreier, Matthew S.</au><au>Hild, Benedikt</au><au>Hafner, Markus</au><au>Wang, David</au><au>Iliev, Iliyan D.</au><au>Belkaid, Yasmine</au><au>Trinchieri, Giorgio</au><au>Rehermann, Barbara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Laboratory mice born to wild mice have natural microbiota and model human immune responses</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2019-08-02</date><risdate>2019</risdate><volume>365</volume><issue>6452</issue><spage>461</spage><epage>461</epage><pages>461-461</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><abstract>Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creating "wildlings." These mice have a natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice. The bacterial microbiome, mycobiome, and virome of wildlings affect the immune landscape of multiple organs. Their gut microbiota outcompete laboratory microbiota and demonstrate resilience to environmental challenges. Wildlings, but not conventional laboratory mice, phenocopied human immune responses in two preclinical studies. A combined natural microbiota- and pathogen-based model may enhance the reproducibility of biomedical studies and increase the bench-to-bedside safety and success of immunological studies.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>31371577</pmid><doi>10.1126/science.aaw4361</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-6154-8924</orcidid><orcidid>https://orcid.org/0000-0002-4336-6518</orcidid><orcidid>https://orcid.org/0000-0002-0369-7371</orcidid><orcidid>https://orcid.org/0000-0002-5781-721X</orcidid><orcidid>https://orcid.org/0000-0003-2645-664X</orcidid><orcidid>https://orcid.org/0000-0002-6989-8686</orcidid><orcidid>https://orcid.org/0000-0001-5892-7464</orcidid><orcidid>https://orcid.org/0000-0002-4948-1023</orcidid><orcidid>https://orcid.org/0000-0002-5662-423X</orcidid><orcidid>https://orcid.org/0000-0001-9962-3571</orcidid><orcidid>https://orcid.org/0000-0003-0884-9749</orcidid><orcidid>https://orcid.org/0000-0001-6832-9951</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2019-08, Vol.365 (6452), p.461-461 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7377314 |
| source | American Association for the Advancement of Science; MEDLINE |
| subjects | Adaptive immunity Animal models Animals Animals, Wild - microbiology Antibiotics Bacteria Blood CD28 antigen Cell activation Clinical trials Cytokines Cytometry Diet Embryos Endotoxemia Environmental conditions Fc receptors Feedback (Response) Fusion protein Gastrointestinal Microbiome Gene sequencing Genetics Genomes Genotype & phenotype Host Microbial Interactions - immunology Host-Pathogen Interactions - immunology Human behavior Human response Humans Immune system Immunity Immunology Immunoregulation Inbreeding Inflammatory diseases Innate immunity Intestinal microflora Laboratories Lymphocytes Lymphocytes T Mammals Medical research Medical treatment Metabolism Mice Mice, Inbred C57BL Microbiota Microorganisms Models, Animal Neurodegenerative diseases Neurological diseases Organs Pathogens Phenotypes Physiology Reproducibility RESEARCH ARTICLE SUMMARY Research facilities Ribonucleic acid RNA Rodents Septic shock Skin Spleen Translation Translational Medical Research - standards Tumor necrosis factor-TNF Vagina |
| title | Laboratory mice born to wild mice have natural microbiota and model human immune responses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T14%3A21%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Laboratory%20mice%20born%20to%20wild%20mice%20have%20natural%20microbiota%20and%20model%20human%20immune%20responses&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Rosshart,%20Stephan%20P.&rft.date=2019-08-02&rft.volume=365&rft.issue=6452&rft.spage=461&rft.epage=461&rft.pages=461-461&rft.issn=0036-8075&rft.eissn=1095-9203&rft_id=info:doi/10.1126/science.aaw4361&rft_dat=%3Cjstor_pubme%3E26762323%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2267785916&rft_id=info:pmid/31371577&rft_jstor_id=26762323&rfr_iscdi=true |