FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.

Fibroblast growth factor 23 (FGF23) is a circulating hormone important in phosphate homeostasis. Abnormal serum levels of FGF23 result in systemic pathologies in humans and mice, including renal phosphate wasting diseases and hyperphosphatemia. We sought to uncover the role FGF23 plays in the audito...

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Autores principales:	Andrew C Lysaght, Quan Yuan, Yi Fan, Neil Kalwani, Paul Caruso, MaryBeth Cunnane, Beate Lanske, Konstantina M Stanković
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf0e45ea0da74dad906e54f2eefd8c43
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spelling	oai:doaj.org-article:bf0e45ea0da74dad906e54f2eefd8c432021-11-25T05:59:54ZFGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.1932-620310.1371/journal.pone.0107681https://doaj.org/article/bf0e45ea0da74dad906e54f2eefd8c432014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107681https://doaj.org/toc/1932-6203Fibroblast growth factor 23 (FGF23) is a circulating hormone important in phosphate homeostasis. Abnormal serum levels of FGF23 result in systemic pathologies in humans and mice, including renal phosphate wasting diseases and hyperphosphatemia. We sought to uncover the role FGF23 plays in the auditory system due to shared molecular mechanisms and genetic pathways between ear and kidney development, the critical roles multiple FGFs play in auditory development and the known hearing phenotype in mice deficient in klotho (KL), a critical co-factor for FGF23 signaling. Using functional assessments of hearing, we demonstrate that Fgf[Formula: see text] mice are profoundly deaf. Fgf[Formula: see text] mice have moderate hearing loss above 20 kHz, consistent with mixed conductive and sensorineural pathology of both middle and inner ear origin. Histology and high-voltage X-ray computed tomography of Fgf[Formula: see text] mice demonstrate dysplastic bulla and ossicles; Fgf[Formula: see text] mice have near-normal morphology. The cochleae of mutant mice appear nearly normal on gross and microscopic inspection. In wild type mice, FGF23 is ubiquitously expressed throughout the cochlea. Measurements from Fgf[Formula: see text] mice do not match the auditory phenotype of Kl-/- mice, suggesting that loss of FGF23 activity impacts the auditory system via mechanisms at least partially independent of KL. Given the extensive middle ear malformations and the overlap of initiation of FGF23 activity and Eustachian tube development, this work suggests a possible role for FGF23 in otitis media.Andrew C LysaghtQuan YuanYi FanNeil KalwaniPaul CarusoMaryBeth CunnaneBeate LanskeKonstantina M StankovićPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107681 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrew C Lysaght Quan Yuan Yi Fan Neil Kalwani Paul Caruso MaryBeth Cunnane Beate Lanske Konstantina M Stanković FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.
description	Fibroblast growth factor 23 (FGF23) is a circulating hormone important in phosphate homeostasis. Abnormal serum levels of FGF23 result in systemic pathologies in humans and mice, including renal phosphate wasting diseases and hyperphosphatemia. We sought to uncover the role FGF23 plays in the auditory system due to shared molecular mechanisms and genetic pathways between ear and kidney development, the critical roles multiple FGFs play in auditory development and the known hearing phenotype in mice deficient in klotho (KL), a critical co-factor for FGF23 signaling. Using functional assessments of hearing, we demonstrate that Fgf[Formula: see text] mice are profoundly deaf. Fgf[Formula: see text] mice have moderate hearing loss above 20 kHz, consistent with mixed conductive and sensorineural pathology of both middle and inner ear origin. Histology and high-voltage X-ray computed tomography of Fgf[Formula: see text] mice demonstrate dysplastic bulla and ossicles; Fgf[Formula: see text] mice have near-normal morphology. The cochleae of mutant mice appear nearly normal on gross and microscopic inspection. In wild type mice, FGF23 is ubiquitously expressed throughout the cochlea. Measurements from Fgf[Formula: see text] mice do not match the auditory phenotype of Kl-/- mice, suggesting that loss of FGF23 activity impacts the auditory system via mechanisms at least partially independent of KL. Given the extensive middle ear malformations and the overlap of initiation of FGF23 activity and Eustachian tube development, this work suggests a possible role for FGF23 in otitis media.
format	article
author	Andrew C Lysaght Quan Yuan Yi Fan Neil Kalwani Paul Caruso MaryBeth Cunnane Beate Lanske Konstantina M Stanković
author_facet	Andrew C Lysaght Quan Yuan Yi Fan Neil Kalwani Paul Caruso MaryBeth Cunnane Beate Lanske Konstantina M Stanković
author_sort	Andrew C Lysaght
title	FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.
title_short	FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.
title_full	FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.
title_fullStr	FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.
title_full_unstemmed	FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.
title_sort	fgf23 deficiency leads to mixed hearing loss and middle ear malformation in mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/bf0e45ea0da74dad906e54f2eefd8c43
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FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.

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