| First Author | Kubinyecz O | Year | 2020 |
| Journal | Front Genet | Volume | 11 |
| Pages | 498 | PubMed ID | 32508883 |
| Mgi Jnum | J:294639 | Mgi Id | MGI:6445336 |
| Doi | 10.3389/fgene.2020.00498 | Citation | Kubinyecz O, et al. (2020) The Jeff Mouse Mutant Model for Chronic Otitis Media Manifests Gain-of-Function as Well as Loss-of-Function Effects. Front Genet 11:498 |
| abstractText | 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 influenzae (NTHi) a proportion of them have inflamed middle ear mucosa and fluid accumulation in the ear suggesting that the Fbxo11 knock-out mice are predisposed to NTHi induced middle ear inflammation. In conclusion, the finding that the phenotype of the Jeff mutant is much more severe than the knock-out indicates that the mutation in Jeff manifests gain-of-function as well as loss-of-function effects at both embryonic and adult stages. |
