Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus.
Typhoid fever and salmonellosis, which are caused by Salmonella Typhi and Typhimurium respectively, are responsible for significant morbidity and mortality in both developed and developing countries. We model typhoid fever using mice infected with Salmonella Typhimurium, which results in a systemic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00375/full |
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| author | Rabia Tahir Khan Rabia Tahir Khan Marie eChevenon Marie eChevenon Kyoko E Yuki Kyoko E Yuki Danielle eMalo Danielle eMalo Danielle eMalo |
| author_facet | Rabia Tahir Khan Rabia Tahir Khan Marie eChevenon Marie eChevenon Kyoko E Yuki Kyoko E Yuki Danielle eMalo Danielle eMalo Danielle eMalo |
| author_sort | Rabia Tahir Khan |
| collection | DOAJ |
| description | Typhoid fever and salmonellosis, which are caused by Salmonella Typhi and Typhimurium respectively, are responsible for significant morbidity and mortality in both developed and developing countries. We model typhoid fever using mice infected with Salmonella Typhimurium, which results in a systemic disease, whereby the outcome of infection is variable in different inbred strains of mice. This model recapitulates several clinical aspects of the human disease and allows the study of the host response to Salmonella Typhimurium infection in vivo. Previous work in our laboratory has identified three loci (Ity, Ity2 and Ity3) in the wild-derived MOLF/Ei mice influencing survival after infection with Salmonella Typhimurium. Fine mapping of the Ity3 locus indicated that two sub-loci contribute collectively to the susceptibility of B6.MOLF-Ity/Ity3 congenic mice to Salmonella infection. In the current paper, we provided further evidence supporting a role for Ncf2 (neutrophil cytosolic factor 2 a subunit of NADPH oxidase) as the gene underlying the Ity3.1 sublocus. Gene expression profiling indicated that the Ity3.1 sub-locus defined a global gene expression signature with networks articulated around Ncf2. Furthermore, based on differential expression and complementation analysis using Selp (Selectin-P) knock-out mice, Selp was identified as a strong candidate gene for the Ity3.2 sub-locus. |
| first_indexed | 2024-04-12T10:48:12Z |
| format | Article |
| id | doaj.art-ad34e1d373234d22baba0924a77421e2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T10:48:12Z |
| publishDate | 2014-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ad34e1d373234d22baba0924a77421e22022-12-22T03:36:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-08-01510.3389/fimmu.2014.00375102522Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus.Rabia Tahir Khan0Rabia Tahir Khan1Marie eChevenon2Marie eChevenon3Kyoko E Yuki4Kyoko E Yuki5Danielle eMalo6Danielle eMalo7Danielle eMalo8McGillMcGill UniversityMcGillMcGill UniversityMcGillMcGill UniversityMcGillMcGill UniversityMcGill UniversityTyphoid fever and salmonellosis, which are caused by Salmonella Typhi and Typhimurium respectively, are responsible for significant morbidity and mortality in both developed and developing countries. We model typhoid fever using mice infected with Salmonella Typhimurium, which results in a systemic disease, whereby the outcome of infection is variable in different inbred strains of mice. This model recapitulates several clinical aspects of the human disease and allows the study of the host response to Salmonella Typhimurium infection in vivo. Previous work in our laboratory has identified three loci (Ity, Ity2 and Ity3) in the wild-derived MOLF/Ei mice influencing survival after infection with Salmonella Typhimurium. Fine mapping of the Ity3 locus indicated that two sub-loci contribute collectively to the susceptibility of B6.MOLF-Ity/Ity3 congenic mice to Salmonella infection. In the current paper, we provided further evidence supporting a role for Ncf2 (neutrophil cytosolic factor 2 a subunit of NADPH oxidase) as the gene underlying the Ity3.1 sublocus. Gene expression profiling indicated that the Ity3.1 sub-locus defined a global gene expression signature with networks articulated around Ncf2. Furthermore, based on differential expression and complementation analysis using Selp (Selectin-P) knock-out mice, Selp was identified as a strong candidate gene for the Ity3.2 sub-locus.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00375/fullSalmonellainnate immunityIty3Murine model for typhoidncf2Selectin P |
| spellingShingle | Rabia Tahir Khan Rabia Tahir Khan Marie eChevenon Marie eChevenon Kyoko E Yuki Kyoko E Yuki Danielle eMalo Danielle eMalo Danielle eMalo Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus. Frontiers in Immunology Salmonella innate immunity Ity3 Murine model for typhoid ncf2 Selectin P |
| title | Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus. |
| title_full | Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus. |
| title_fullStr | Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus. |
| title_full_unstemmed | Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus. |
| title_short | Genetic dissection of the Ity3 locus identifies a role for Ncf2 co-expression modules and suggests Selp as a candidate gene underlying the Ity3.2 locus. |
| title_sort | genetic dissection of the ity3 locus identifies a role for ncf2 co expression modules and suggests selp as a candidate gene underlying the ity3 2 locus |
| topic | Salmonella innate immunity Ity3 Murine model for typhoid ncf2 Selectin P |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00375/full |
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