AUTHOR=Vikhe Pratik P. , Tateossian Hilda , Bharj Gurpreet , Brown Steve D.M. , Hood Derek W. 

TITLE=Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00050

DOI=10.3389/fgene.2020.00050

ISSN=1664-8021

ABSTRACT=<p>The <italic>Jeff</italic> mouse mutant carries a mutation in the F-box only 11 gene (<italic>Fbxo11</italic>) and heterozygous animals display conductive deafness due to the development of otitis media (OM). The <italic>Fbxo11</italic> locus is also associated with chronic otitis media with effusion (COME) and recurrent OM in humans. The <italic>Jeff</italic> 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 <italic>Jeff</italic> mutation on the immune cell content using multicolor flow cytometry. In blood of <italic>Jeff</italic> 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 <italic>Jeff</italic> heterozygotes, with a concomitant reduction in B-lymphocytes and T-cytotoxic cells. In the spleen, <italic>Jeff</italic> 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 <italic>Jeff</italic> heterozygote mice. Similar analysis carried out on <italic>Fbxo11<sup>tm2b/+</sup></italic> 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 <italic>Jeff</italic> heterozygote serum compared to wild-type. This analysis increases our understanding of the role played by <italic>Fbxo11</italic>, a gene associated with human OM, in the systemic and localized cellular immune response associated with increased susceptibility to OM.</p>