{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:11:03Z","timestamp":1772169063373,"version":"3.50.1"},"reference-count":39,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T00:00:00Z","timestamp":1566259200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["FC001076"],"award-info":[{"award-number":["FC001076"]}]},{"name":"Wellcome Trust","award":["091664"],"award-info":[{"award-number":["091664"]}]},{"DOI":"10.13039\/501100001645","name":"Boehringer Ingelheim Fonds","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001645","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Health","award":["AI103197"],"award-info":[{"award-number":["AI103197"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background<\/ns4:bold>\n                    : Infections cause the production of inflammatory cytokines such as Interferon gamma (IFN\u03b3). IFN\u03b3 in turn prompts the upregulation of a range of host defence proteins including members of the family of guanylate binding proteins (Gbps). In humans and mice alike, GBPs restrict the intracellular replication of invasive microbes and promote inflammation. To study the physiological functions of Gbp family members, the most commonly chosen\n                    <ns4:italic>in vivo<\/ns4:italic>\n                    models are mice harbouring loss-of-function mutations in either individual\n                    <ns4:italic>Gbp<\/ns4:italic>\n                    genes or the entire\n                    <ns4:italic>Gbp<\/ns4:italic>\n                    gene cluster on mouse chromosome 3. Individual\n                    <ns4:italic>Gbp<\/ns4:italic>\n                    deletion strains differ in their design, as some strains exist on a pure C57BL\/6 genetic background, while other strains contain a 129-derived genetic interval encompassing the\n                    <ns4:italic>Gbp<\/ns4:italic>\n                    gene cluster on an otherwise C57BL\/6 genetic background.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods<\/ns4:bold>\n                    : To determine whether the presence of 129 alleles of paralogous\n                    <ns4:italic>Gbps<\/ns4:italic>\n                    could influence the phenotypes of 129-congenic\n                    <ns4:italic>Gbp<\/ns4:italic>\n                    -deficient strains, we studied the expression of Gbps in both C57BL\/6J and 129\/Sv mice following\n                    <ns4:italic>in vivo<\/ns4:italic>\n                    stimulation with adjuvants and after infection with either\n                    <ns4:italic>Toxoplasma<\/ns4:italic>\n                    <ns4:italic>gondii<\/ns4:italic>\n                    or\n                    <ns4:italic>Shigella flexneri<\/ns4:italic>\n                    .\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results<\/ns4:bold>\n                    : We show that C57BL\/6J relative to 129\/Sv mice display moderately elevated expression of Gbp2, but more prominently, are also defective for Gbp2b (formerly Gbp1) mRNA induction upon immune priming. Notably,\n                    <ns4:italic>Toxoplasma<\/ns4:italic>\n                    infections induce robust Gbp2b protein expression in both strains of mice, suggestive of a\n                    <ns4:italic>Toxoplasma<\/ns4:italic>\n                    -activated mechanism driving Gbp2b protein translation. We further find that the higher expression of Gbp2b mRNA in 129\/Sv mice correlates with a gene duplication event at the\n                    <ns4:italic>Gbp2b<\/ns4:italic>\n                    locus resulting in two copies of the\n                    <ns4:italic>Gbp2b<\/ns4:italic>\n                    gene on the haploid genome of the 129\/Sv strain.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions<\/ns4:bold>\n                    : Our findings demonstrate functional differences between 129 and C57BL\/6\n                    <ns4:italic>Gbp<\/ns4:italic>\n                    alleles which need to be considered in the design and interpretation of studies utilizing mouse models, particularly for phenotypes influenced by Gbp2 or Gbp2b expression.\n                  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T.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-0367","authenticated-orcid":false,"given":"Daniel","family":"Fisch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-7940","authenticated-orcid":false,"given":"Harshil","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8707-4608","authenticated-orcid":false,"given":"J\u00f6rn","family":"Coers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-3442","authenticated-orcid":false,"given":"Eva-Maria","family":"Frickel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,8,20]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"50-62","DOI":"10.4161\/auto.22482","article-title":"Autophagy 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16734.r36267, Peter Staeheli, Faculty of Medicine, University of Freiburg, Freiburg, Germany, 23 Aug 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-124\/v1#referee-response-36267","order":0,"name":"referee-response-36267","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16734.r36269, Igor Kramnik, National Emerging Infectious Diseases Laboratory, Boston University School of Medicine, Boston, MA, USA, 17 Sep 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-124\/v1#referee-response-36269","order":1,"name":"referee-response-36269","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust through a Career Development Fellowship to EMF [091664] and core funding to the Francis Crick Institute. \nThe Francis Crick Institute receives its core funding from Cancer Research UK [FC001076], the UK Medical Research Council [FC001076], and the Wellcome Trust [FC001076]. DF was supported by a Boehringer Ingelheim Fonds PhD fellowship. This work was supported by a National Institute Health grant to JC [AI103197]. JC holds an Investigator in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}