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Document 1 of 1

Genetic Background of Prop1 ^sup df^ Mutants Provides Remarkable

Protection Against Hypothyroidism-Induced Hearing Impairment
Author: Fang, Qing; Giordimaina, Alicia M; Dolan, David F; Camper, Sally A; Mustapha, Mirna
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Abstract: Hypothyroidism is a cause of genetic and environmentally induced deafness. The
sensitivity of cochlear development and function to thyroid hormone (TH) mandates
understanding TH action in this sensory organ. Prop1 ^sup df^ and Pou1f1 ^sup dw^ mutant
mice carry mutations in different pituitary transcription factors, each resulting in pituitary
thyrotropin deficiency. Despite the same lack of detectable serum TH, these mutants have very
different hearing abilities: Prop1 ^sup df^ mutants are mildly affected, while Pou1f1 ^sup dw^
mutants are completely deaf. Genetic studies show that this difference is attributable to the
genetic backgrounds. Using embryo transfer, we discovered that factors intrinsic to the fetus are
the major contributor to this difference, not maternal effects. We analyzed Prop1 ^sup df^
mutants to identify processes in cochlear development that are disrupted in other hypothyroid
animal models but protected in Prop1 ^sup df^ mutants by the genetic background. The
development of outer hair cell (OHC) function is delayed, but Prestin and KCNQ4 immunostaining
appear normal in mature Prop1 ^sup df^ mutants. The endocochlear potential and KCNJ10
immunostaining in the stria vascularis are indistinguishable from wild type, and no differences in
neurofilament or synaptophysin staining are evident in Prop1 ^sup df^ mutants. The synaptic
vesicle protein otoferlin normally shifts expression from OHC to IHC as temporary afferent fibers
beneath the OHC regress postnatally. Prop1 ^sup df^ mutants exhibit persistent, abnormal
expression of otoferlin in apical OHC, suggesting delayed maturation of synaptic function. Thus,
the genetic background of Prop1 ^sup df^ mutants is remarkably protective for most functions
affected in other hypothyroid mice. The Prop1 ^sup df^ mutant is an attractive model for
identifying the genes that protect against deafness.[PUBLICATION ABSTRACT]

MeSH: Animals, Female, Hair Cells, Auditory, Outer -- physiology, KCNQ Potassium Channels -genetics, Membrane Proteins -- analysis, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mutation,
Potassium Channels, Inwardly Rectifying -- analysis, Pregnancy, Thyroid Hormones -- physiology,
Transcription Factor Pit-1 -- genetics, Hearing Loss -- prevention & control (major), Homeodomain
Proteins -- genetics (major), Hypothyroidism -- complications (major)
Substance: Homeodomain Proteins; KCNQ Potassium Channels; Kcnq4 protein, mouse; Membrane
Proteins; Pit1 protein, mouse; Potassium Channels, Inwardly Rectifying; Prophet of Pit-1 protein;
Thyroid Hormones; Transcription Factor Pit-1; otoferlin protein, mouse; potassium inwardlyrectifying channel, subfamily J, member 10;
Publication title: Journal of the Association for Research in Otolaryngology
Volume: 13
Issue: 2
Pages: 173-84
Publication year: 2012
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Publication date: Apr 2012

Year: 2012
Publisher: Springer Science & Business Media
Place of publication: New York
Country of publication: Netherlands
Publication subject: Medical Sciences--Otorhinolaryngology
ISSN: 15253961
Source type: Scholarly Journals
Language of publication: English
Document type: Feature, Journal Article
DOI: http://dx.doi.org/10.1007/s10162-011-0302-3
Accession number: 22143287
ProQuest document ID: 927009144
Document URL: http://search.proquest.com/docview/927009144?accountid=33171
Copyright: Association for Research in Otolaryngology 2012
Last updated: 2014-03-06
Database: ProQuest Medical Library,ProQuest Nursing & Allied Health Source

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