Abstract
Chronic otitis media (OM) is the most common cause of hearing loss worldwide, yet the underlying genetics and molecular pathology are poorly understood. The mouse mutant Jeff is a single gene mouse model for OM identified from a deafness screen as part of an ENU mutagenesis program at MRC Harwell. Jeff carries a missense mutation in the Fbxo11 gene. Jeff heterozygotes (Fbxo11 Jf/+ ) develop chronic OM at weaning and have reduced hearing. Homozygotes (Fbxo11 Jf/Jf ) display perinatal lethality due to developmental epithelial abnormalities. In order to investigate the role of FBXO11 and the type of mutation responsible for the phenotype of the Jeff mice, a knock-out mouse model was created and compared to Jeff. Surprisingly, the heterozygote knock-outs (Fbxo11 tm2b/+ ) show a much milder phenotype: they do not display any auditory deficit and only some of them have thickened middle ear epithelial lining with no fluid in the ear. In addition, the knock-out homozygote embryos (Fbxo11 tm2b/tm2b ), as well as the compound heterozygotes (Fbxo11 tm2b/Jf ) show only mild abnormalities compared to Jeff homozygotes (Fbxo11 Jf/Jf ). Interestingly, 3 days after intranasal inoculation of the Fbxo11 tm2b/+ mice with non-typeable Haemophilus i...Continue Reading
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