C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved]
Background: Infections cause the production of inflammatory cytokines such as Interferon gamma (IFNγ). IFNγ 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 intracell...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wellcome
2019-08-01
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| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/4-124/v1 |
| _version_ | 1818951753534537728 |
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| author | Barbara Clough Ryan Finethy Rabia T. Khan Daniel Fisch Sarah Jordan Harshil Patel Jörn Coers Eva-Maria Frickel |
| author_facet | Barbara Clough Ryan Finethy Rabia T. Khan Daniel Fisch Sarah Jordan Harshil Patel Jörn Coers Eva-Maria Frickel |
| author_sort | Barbara Clough |
| collection | DOAJ |
| description | Background: Infections cause the production of inflammatory cytokines such as Interferon gamma (IFNγ). IFNγ 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 in vivo models are mice harbouring loss-of-function mutations in either individual Gbp genes or the entire Gbp gene cluster on mouse chromosome 3. Individual Gbp 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 Gbp gene cluster on an otherwise C57BL/6 genetic background. Methods: To determine whether the presence of 129 alleles of paralogous Gbps could influence the phenotypes of 129-congenic Gbp-deficient strains, we studied the expression of Gbps in both C57BL/6J and 129/Sv mice following in vivo stimulation with adjuvants and after infection with either Toxoplasma gondii or Shigella flexneri. Results: 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, Toxoplasma infections induce robust Gbp2b protein expression in both strains of mice, suggestive of a Toxoplasma-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 Gbp2b locus resulting in two copies of the Gbp2b gene on the haploid genome of the 129/Sv strain. Conclusions: Our findings demonstrate functional differences between 129 and C57BL/6 Gbp 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. |
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| format | Article |
| id | doaj.art-4b6a1ef71eb04f5688dc8cf72c9cb390 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-20T09:39:30Z |
| publishDate | 2019-08-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-4b6a1ef71eb04f5688dc8cf72c9cb3902022-12-21T19:44:56ZengWellcomeWellcome Open Research2398-502X2019-08-01410.12688/wellcomeopenres.15329.116734C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved]Barbara Clough0Ryan Finethy1Rabia T. Khan2Daniel Fisch3Sarah Jordan4Harshil Patel5Jörn Coers6Eva-Maria Frickel7Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London, NW1 1AT, UKDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USAHost-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London, NW1 1AT, UKHost-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London, NW1 1AT, UKHost-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London, NW1 1AT, UKBioinformatics and Biostatistics, The Francis Crick Institute, London, NW1 1AT, UKDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USAHost-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London, NW1 1AT, UKBackground: Infections cause the production of inflammatory cytokines such as Interferon gamma (IFNγ). IFNγ 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 in vivo models are mice harbouring loss-of-function mutations in either individual Gbp genes or the entire Gbp gene cluster on mouse chromosome 3. Individual Gbp 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 Gbp gene cluster on an otherwise C57BL/6 genetic background. Methods: To determine whether the presence of 129 alleles of paralogous Gbps could influence the phenotypes of 129-congenic Gbp-deficient strains, we studied the expression of Gbps in both C57BL/6J and 129/Sv mice following in vivo stimulation with adjuvants and after infection with either Toxoplasma gondii or Shigella flexneri. Results: 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, Toxoplasma infections induce robust Gbp2b protein expression in both strains of mice, suggestive of a Toxoplasma-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 Gbp2b locus resulting in two copies of the Gbp2b gene on the haploid genome of the 129/Sv strain. Conclusions: Our findings demonstrate functional differences between 129 and C57BL/6 Gbp 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.https://wellcomeopenresearch.org/articles/4-124/v1 |
| spellingShingle | Barbara Clough Ryan Finethy Rabia T. Khan Daniel Fisch Sarah Jordan Harshil Patel Jörn Coers Eva-Maria Frickel C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved] Wellcome Open Research |
| title | C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved] |
| title_full | C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved] |
| title_fullStr | C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved] |
| title_full_unstemmed | C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved] |
| title_short | C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved] |
| title_sort | c57bl 6 and 129 inbred mouse strains differ in gbp2 and gbp2b expression in response to inflammatory stimuli in vivo version 1 peer review 2 approved |
| url | https://wellcomeopenresearch.org/articles/4-124/v1 |
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