Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media
The Jeff mouse mutant carries a mutation in the F-box only 11 gene (Fbxo11) and heterozygous animals display conductive deafness due to the development of otitis media (OM). The Fbxo11 locus is also associated with chronic otitis media with effusion (COME) and recurrent OM in humans. The Jeff mutati...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00050/full |
| _version_ | 1818216422438862848 |
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| author | Pratik P. Vikhe Hilda Tateossian Gurpreet Bharj Steve D.M. Brown Derek W. Hood |
| author_facet | Pratik P. Vikhe Hilda Tateossian Gurpreet Bharj Steve D.M. Brown Derek W. Hood |
| author_sort | Pratik P. Vikhe |
| collection | DOAJ |
| description | The Jeff mouse mutant carries a mutation in the F-box only 11 gene (Fbxo11) and heterozygous animals display conductive deafness due to the development of otitis media (OM). The Fbxo11 locus is also associated with chronic otitis media with effusion (COME) and recurrent OM in humans. The Jeff mutation affects the ability of FBXO11 to stabilize p53 that leads to perturbation in the TGF-beta/Smad2 signaling pathway important in immunity and inflammation. In the current study, we evaluated the effect of the Jeff mutation on the immune cell content using multicolor flow cytometry. In blood of Jeff heterozygotes, we observed a significant increase in the number of NK, dendritic (CD11b+), neutrophils, and natural killer T (NKT) cells and a significant decrease in effector T-helper and B-lymphocytes compared to wild-type controls. The percentage of NK cells significantly decreased in the lungs of Jeff heterozygotes, with a concomitant reduction in B-lymphocytes and T-cytotoxic cells. In the spleen, Jeff heterozygotes displayed a significant decrease in mature B-lymphocytes, effector T-helper, and naïve T-cytotoxic cells. Neutrophils, dendritic, and NKT cells dominated bulla fluid in Jeff heterozygote mice. Similar analysis carried out on Fbxo11tm2b/+ heterozygotes, which carry a null allele, showed no difference when compared to wild-type. Cytokine/chemokine analysis revealed a significant increase in the G-CSF, GM-CSF, sTNFRI, TPO, and IL-7 levels in Jeff heterozygote serum compared to wild-type. This analysis increases our understanding of the role played by Fbxo11, a gene associated with human OM, in the systemic and localized cellular immune response associated with increased susceptibility to OM. |
| first_indexed | 2024-12-12T06:51:43Z |
| format | Article |
| id | doaj.art-fbd51b26323b4a8c8438e58f67966add |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-12T06:51:43Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-fbd51b26323b4a8c8438e58f67966add2022-12-22T00:34:03ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-02-011110.3389/fgene.2020.00050486938Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis MediaPratik P. VikheHilda TateossianGurpreet BharjSteve D.M. BrownDerek W. HoodThe Jeff mouse mutant carries a mutation in the F-box only 11 gene (Fbxo11) and heterozygous animals display conductive deafness due to the development of otitis media (OM). The Fbxo11 locus is also associated with chronic otitis media with effusion (COME) and recurrent OM in humans. The Jeff mutation affects the ability of FBXO11 to stabilize p53 that leads to perturbation in the TGF-beta/Smad2 signaling pathway important in immunity and inflammation. In the current study, we evaluated the effect of the Jeff mutation on the immune cell content using multicolor flow cytometry. In blood of Jeff heterozygotes, we observed a significant increase in the number of NK, dendritic (CD11b+), neutrophils, and natural killer T (NKT) cells and a significant decrease in effector T-helper and B-lymphocytes compared to wild-type controls. The percentage of NK cells significantly decreased in the lungs of Jeff heterozygotes, with a concomitant reduction in B-lymphocytes and T-cytotoxic cells. In the spleen, Jeff heterozygotes displayed a significant decrease in mature B-lymphocytes, effector T-helper, and naïve T-cytotoxic cells. Neutrophils, dendritic, and NKT cells dominated bulla fluid in Jeff heterozygote mice. Similar analysis carried out on Fbxo11tm2b/+ heterozygotes, which carry a null allele, showed no difference when compared to wild-type. Cytokine/chemokine analysis revealed a significant increase in the G-CSF, GM-CSF, sTNFRI, TPO, and IL-7 levels in Jeff heterozygote serum compared to wild-type. This analysis increases our understanding of the role played by Fbxo11, a gene associated with human OM, in the systemic and localized cellular immune response associated with increased susceptibility to OM.https://www.frontiersin.org/article/10.3389/fgene.2020.00050/fullFbxo11otitis mediaJeff mouseimmune cellsnatural killer cells |
| spellingShingle | Pratik P. Vikhe Hilda Tateossian Gurpreet Bharj Steve D.M. Brown Derek W. Hood Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media Frontiers in Genetics Fbxo11 otitis media Jeff mouse immune cells natural killer cells |
| title | Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media |
| title_full | Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media |
| title_fullStr | Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media |
| title_full_unstemmed | Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media |
| title_short | Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media |
| title_sort | mutation in fbxo11 leads to altered immune cell content in jeff mouse model of otitis media |
| topic | Fbxo11 otitis media Jeff mouse immune cells natural killer cells |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00050/full |
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