A mouse model with postnatal endolymphatic hydrops and hearing loss

Cliff A. Megerian; Maroun T. Semaan; Saba Aftab; Lauren B. Kisley; Qing Yin Zheng; Karen S. Pawlowski; Charles G. Wright; Kumar N. Alagramam

doi:10.1016/j.heares.2008.01.002

A mouse model with postnatal endolymphatic hydrops and hearing loss

Cliff A. Megerian, Maroun T. Semaan, Saba Aftab, Lauren B. Kisley, Qing Yin Zheng, Karen S. Pawlowski, Charles G. Wright, Kumar N. Alagramam

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	90-105
Number of pages	16
Journal	Hearing Research
Volume	237
Issue number	1-2
DOIs	https://doi.org/10.1016/j.heares.2008.01.002
State	Published - Mar 2008

Keywords

Endolymphatic hydrops
Meniere's disease
Phex mutant

ASJC Scopus subject areas

Sensory Systems

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10.1016/j.heares.2008.01.002

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@article{da3fcc75868c4f7fb5dba835bfacc9e0,

title = "A mouse model with postnatal endolymphatic hydrops and hearing loss",

abstract = "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 PhexHyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (PhexHyp-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 PhexHyp-Duk/Y mice and to test the hypotheses that (a) the PhexHyp-Duk/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the PhexHyp-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 PhexHyp-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, PhexHyp-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.",

keywords = "Endolymphatic hydrops, Meniere's disease, Phex mutant",

author = "Megerian, {Cliff A.} and Semaan, {Maroun T.} and Saba Aftab and Kisley, {Lauren B.} and Zheng, {Qing Yin} and Pawlowski, {Karen S.} and Wright, {Charles G.} and Alagramam, {Kumar N.}",

note = "Funding Information: We would like to thank Dr. Brian McDermott and Chris Heddon for critical reading of this manuscript. This work was supported by grants to Drs. Alagramam and Megerian from Rainbow Board of Trustees, Rainbow Babies and Children{\textquoteright}s Hospitals, University Hospitals Case Medical Center.",

year = "2008",

month = mar,

doi = "10.1016/j.heares.2008.01.002",

language = "English (US)",

volume = "237",

pages = "90--105",

journal = "Hearing Research",

issn = "0378-5955",

publisher = "Elsevier",

number = "1-2",

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TY - JOUR

T1 - A mouse model with postnatal endolymphatic hydrops and hearing loss

AU - Megerian, Cliff A.

AU - Semaan, Maroun T.

AU - Aftab, Saba

AU - Kisley, Lauren B.

AU - Zheng, Qing Yin

AU - Pawlowski, Karen S.

AU - Wright, Charles G.

AU - Alagramam, Kumar N.

N1 - Funding Information: We would like to thank Dr. Brian McDermott and Chris Heddon for critical reading of this manuscript. This work was supported by grants to Drs. Alagramam and Megerian from Rainbow Board of Trustees, Rainbow Babies and Children’s Hospitals, University Hospitals Case Medical Center.

PY - 2008/3

Y1 - 2008/3

N2 - 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 PhexHyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (PhexHyp-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 PhexHyp-Duk/Y mice and to test the hypotheses that (a) the PhexHyp-Duk/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the PhexHyp-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 PhexHyp-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, PhexHyp-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.

AB - 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 PhexHyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (PhexHyp-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 PhexHyp-Duk/Y mice and to test the hypotheses that (a) the PhexHyp-Duk/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the PhexHyp-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 PhexHyp-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, PhexHyp-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.

KW - Endolymphatic hydrops

KW - Meniere's disease

KW - Phex mutant

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A mouse model with postnatal endolymphatic hydrops and hearing loss

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Keywords

ASJC Scopus subject areas

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