| First Author | Megerian CA | Year | 2008 |
| Journal | Hear Res | Volume | 237 |
| Issue | 1-2 | Pages | 90-105 |
| PubMed ID | 18289812 | Mgi Jnum | J:132678 |
| Mgi Id | MGI:3776679 | Doi | 10.1016/j.heares.2008.01.002 |
| Citation | Megerian CA, et al. (2008) A mouse model with postnatal endolymphatic hydrops and hearing loss. Hear Res 237(1-2):90-105 |
| abstractText | Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere's disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex(Hyp-Duk) mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (Phex(Hyp-Duk)/Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex(Hyp-Duk)/Y mice and to test the hypotheses that (a) the Phex(Hyp-Duk)/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex(Hyp-Duk)/Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex(Hyp-Duk)/Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex(Hyp-Duk)/Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients. |
