GlutaredoxinV1, Main, Exploration, bibRecord, 000254

Grxcr2 is required for stereocilia morphogenesis in the cochlea.

Identifieur interne : 000254 ( Main/Exploration ); précédent : 000253; suivant : 000255

Grxcr2 is required for stereocilia morphogenesis in the cochlea.

Auteurs : Matthew R. Avenarius [États-Unis] ; Jae-Yun Jung [États-Unis] ; Charles Askew [États-Unis] ; Sherri M. Jones [États-Unis] ; Kristina L. Hunker [États-Unis] ; Hela Azaiez [États-Unis] ; Atteeq U. Rehman [États-Unis] ; Margit Schraders [Pays-Bas] ; Hossein Najmabadi [Iran] ; Hannie Kremer [Pays-Bas] ; Richard J H. Smith [États-Unis] ; Gwenaëlle S G. Géléoc [États-Unis] ; David F. Dolan [États-Unis] ; Yehoash Raphael [États-Unis] ; David C. Kohrman [États-Unis]

Source :

PloS one [ 1932-6203 ] ; 2018.

RBID : pubmed:30157177

Descripteurs français

KwdFr :
- Animaux (MeSH), Cochlée (croissance et développement), Cochlée (cytologie), Conformation des protéines (MeSH), Glutarédoxines (composition chimique), Glutarédoxines (génétique), Glutarédoxines (métabolisme), Humains (MeSH), Locus génétiques (génétique), Modèles moléculaires (MeSH), Morphogenèse (MeSH), Mutation (MeSH), Mécanotransduction cellulaire (MeSH), Perte d'audition (anatomopathologie), Perte d'audition (génétique), Régulation de l'expression des gènes au cours du développement (MeSH), Souris (MeSH), Spécificité d'espèce (MeSH), Stéréocils (métabolisme), Séquence d'acides aminés (MeSH).
MESH :
- anatomopathologie : Perte d'audition.
- composition chimique : Glutarédoxines.
- croissance et développement : Cochlée.
- cytologie : Cochlée.
- génétique : Glutarédoxines, Locus génétiques, Perte d'audition.
- métabolisme : Glutarédoxines, Stéréocils.
- Animaux, Conformation des protéines, Humains, Modèles moléculaires, Morphogenèse, Mutation, Mécanotransduction cellulaire, Régulation de l'expression des gènes au cours du développement, Souris, Spécificité d'espèce, Séquence d'acides aminés.

English descriptors

KwdEn :
- Amino Acid Sequence (MeSH), Animals (MeSH), Cochlea (cytology), Cochlea (growth & development), Gene Expression Regulation, Developmental (MeSH), Genetic Loci (genetics), Glutaredoxins (chemistry), Glutaredoxins (genetics), Glutaredoxins (metabolism), Hearing Loss (genetics), Hearing Loss (pathology), Humans (MeSH), Mechanotransduction, Cellular (MeSH), Mice (MeSH), Models, Molecular (MeSH), Morphogenesis (MeSH), Mutation (MeSH), Protein Conformation (MeSH), Species Specificity (MeSH), Stereocilia (metabolism).
MESH :
- chemical , chemistry : Glutaredoxins.
- cytology : Cochlea.
- genetics : Genetic Loci, Glutaredoxins, Hearing Loss.
- growth & development : Cochlea.
- chemical , metabolism : Glutaredoxins, Stereocilia.
- pathology : Hearing Loss.
- Amino Acid Sequence, Animals, Gene Expression Regulation, Developmental, Humans, Mechanotransduction, Cellular, Mice, Models, Molecular, Morphogenesis, Mutation, Protein Conformation, Species Specificity.

Abstract

Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dimensions during development. In this study, we analyzed expression of the paralog Grxcr2 in the mouse and evaluated auditory and vestibular function of strains carrying targeted mutations of the gene. Peak expression of Grxcr2 occurs during early postnatal development of the inner ear and GRXCR2 is localized to stereocilia in both the cochlea and in vestibular organs. Homozygous Grxcr2 deletion mutants exhibit significant hearing loss by 3 weeks of age that is associated with developmental defects in stereocilia bundle orientation and organization. Despite these bundle defects, the mechanotransduction apparatus assembles in relatively normal fashion as determined by whole cell electrophysiological evaluation and FM1-43 uptake. Although Grxcr2 mutants do not exhibit overt vestibular dysfunction, evaluation of vestibular evoked potentials revealed subtle defects of the mutants in response to linear accelerations. In addition, reduced Grxcr2 expression in a hypomorphic mutant strain is associated with progressive hearing loss and bundle defects. The stereocilia localization of GRXCR2, together with the bundle pathologies observed in the mutants, indicate that GRXCR2 plays an intrinsic role in bundle orientation, organization, and sensory function in the inner ear during development and at maturity.

DOI: 10.1371/journal.pone.0201713
PubMed: 30157177
PubMed Central: PMC6114524

Affiliations:

Iran, Pays-Bas, États-Unis
Caroline du Nord, Gueldre, Iowa, Maryland, Massachusetts, Michigan, Virginie
Iowa City, Nimègue
Université de l'Iowa

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000218
to stream Main, to step Curation: 000218

Le document en format XML

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</placeName>
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<affiliation wicri:level="2"><nlm:affiliation>Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.</nlm:affiliation>
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<author><name sortKey="Hunker, Kristina L" sort="Hunker, Kristina L" uniqKey="Hunker K" first="Kristina L" last="Hunker">Kristina L. Hunker</name>
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<author><name sortKey="Rehman, Atteeq U" sort="Rehman, Atteeq U" uniqKey="Rehman A" first="Atteeq U" last="Rehman">Atteeq U. Rehman</name>
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<author><name sortKey="Schraders, Margit" sort="Schraders, Margit" uniqKey="Schraders M" first="Margit" last="Schraders">Margit Schraders</name>
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<author><name sortKey="Najmabadi, Hossein" sort="Najmabadi, Hossein" uniqKey="Najmabadi H" first="Hossein" last="Najmabadi">Hossein Najmabadi</name>
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<author><name sortKey="Kremer, Hannie" sort="Kremer, Hannie" uniqKey="Kremer H" first="Hannie" last="Kremer">Hannie Kremer</name>
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<wicri:regionArea>Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen</wicri:regionArea>
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</placeName>
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<affiliation wicri:level="3"><nlm:affiliation>Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
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</placeName>
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<author><name sortKey="Smith, Richard J H" sort="Smith, Richard J H" uniqKey="Smith R" first="Richard J H" last="Smith">Richard J H. Smith</name>
<affiliation wicri:level="4"><nlm:affiliation>Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<settlement type="city">Iowa City</settlement>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
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<author><name sortKey="Geleoc, Gwenaelle S G" sort="Geleoc, Gwenaelle S G" uniqKey="Geleoc G" first="Gwenaëlle S G" last="Géléoc">Gwenaëlle S G. Géléoc</name>
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<author><name sortKey="Dolan, David F" sort="Dolan, David F" uniqKey="Dolan D" first="David F" last="Dolan">David F. Dolan</name>
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</placeName>
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<author><name sortKey="Raphael, Yehoash" sort="Raphael, Yehoash" uniqKey="Raphael Y" first="Yehoash" last="Raphael">Yehoash Raphael</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kohrman, David C" sort="Kohrman, David C" uniqKey="Kohrman D" first="David C" last="Kohrman">David C. Kohrman</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2018">2018</date>
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<idno type="doi">10.1371/journal.pone.0201713</idno>
<idno type="pmc">PMC6114524</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Grxcr2 is required for stereocilia morphogenesis in the cochlea.</title>
<author><name sortKey="Avenarius, Matthew R" sort="Avenarius, Matthew R" uniqKey="Avenarius M" first="Matthew R" last="Avenarius">Matthew R. Avenarius</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jung, Jae Yun" sort="Jung, Jae Yun" uniqKey="Jung J" first="Jae-Yun" last="Jung">Jae-Yun Jung</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Askew, Charles" sort="Askew, Charles" uniqKey="Askew C" first="Charles" last="Askew">Charles Askew</name>
<affiliation wicri:level="2"><nlm:affiliation>Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jones, Sherri M" sort="Jones, Sherri M" uniqKey="Jones S" first="Sherri M" last="Jones">Sherri M. Jones</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Communication Sciences and Disorders, East Carolina University, Greenville, North Carolina, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Communication Sciences and Disorders, East Carolina University, Greenville, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hunker, Kristina L" sort="Hunker, Kristina L" uniqKey="Hunker K" first="Kristina L" last="Hunker">Kristina L. Hunker</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Azaiez, Hela" sort="Azaiez, Hela" uniqKey="Azaiez H" first="Hela" last="Azaiez">Hela Azaiez</name>
<affiliation wicri:level="4"><nlm:affiliation>Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa</wicri:regionArea>
<placeName><region type="state">Iowa</region>
<settlement type="city">Iowa City</settlement>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
</author>
<author><name sortKey="Rehman, Atteeq U" sort="Rehman, Atteeq U" uniqKey="Rehman A" first="Atteeq U" last="Rehman">Atteeq U. Rehman</name>
<affiliation wicri:level="2"><nlm:affiliation>Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schraders, Margit" sort="Schraders, Margit" uniqKey="Schraders M" first="Margit" last="Schraders">Margit Schraders</name>
<affiliation wicri:level="3"><nlm:affiliation>Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Human Genetics, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Najmabadi, Hossein" sort="Najmabadi, Hossein" uniqKey="Najmabadi H" first="Hossein" last="Najmabadi">Hossein Najmabadi</name>
<affiliation wicri:level="1"><nlm:affiliation>Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.</nlm:affiliation>
<country xml:lang="fr">Iran</country>
<wicri:regionArea>Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran</wicri:regionArea>
<wicri:noRegion>Tehran</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kremer, Hannie" sort="Kremer, Hannie" uniqKey="Kremer H" first="Hannie" last="Kremer">Hannie Kremer</name>
<affiliation wicri:level="3"><nlm:affiliation>Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Human Genetics, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, Richard J H" sort="Smith, Richard J H" uniqKey="Smith R" first="Richard J H" last="Smith">Richard J H. Smith</name>
<affiliation wicri:level="4"><nlm:affiliation>Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa</wicri:regionArea>
<placeName><region type="state">Iowa</region>
<settlement type="city">Iowa City</settlement>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
</author>
<author><name sortKey="Geleoc, Gwenaelle S G" sort="Geleoc, Gwenaelle S G" uniqKey="Geleoc G" first="Gwenaëlle S G" last="Géléoc">Gwenaëlle S G. Géléoc</name>
<affiliation wicri:level="2"><nlm:affiliation>Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dolan, David F" sort="Dolan, David F" uniqKey="Dolan D" first="David F" last="Dolan">David F. Dolan</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Raphael, Yehoash" sort="Raphael, Yehoash" uniqKey="Raphael Y" first="Yehoash" last="Raphael">Yehoash Raphael</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kohrman, David C" sort="Kohrman, David C" uniqKey="Kohrman D" first="David C" last="Kohrman">David C. Kohrman</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PloS one</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2018" type="published">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence (MeSH)</term>
<term>Animals (MeSH)</term>
<term>Cochlea (cytology)</term>
<term>Cochlea (growth & development)</term>
<term>Gene Expression Regulation, Developmental (MeSH)</term>
<term>Genetic Loci (genetics)</term>
<term>Glutaredoxins (chemistry)</term>
<term>Glutaredoxins (genetics)</term>
<term>Glutaredoxins (metabolism)</term>
<term>Hearing Loss (genetics)</term>
<term>Hearing Loss (pathology)</term>
<term>Humans (MeSH)</term>
<term>Mechanotransduction, Cellular (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Models, Molecular (MeSH)</term>
<term>Morphogenesis (MeSH)</term>
<term>Mutation (MeSH)</term>
<term>Protein Conformation (MeSH)</term>
<term>Species Specificity (MeSH)</term>
<term>Stereocilia (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Cochlée (croissance et développement)</term>
<term>Cochlée (cytologie)</term>
<term>Conformation des protéines (MeSH)</term>
<term>Glutarédoxines (composition chimique)</term>
<term>Glutarédoxines (génétique)</term>
<term>Glutarédoxines (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Locus génétiques (génétique)</term>
<term>Modèles moléculaires (MeSH)</term>
<term>Morphogenèse (MeSH)</term>
<term>Mutation (MeSH)</term>
<term>Mécanotransduction cellulaire (MeSH)</term>
<term>Perte d'audition (anatomopathologie)</term>
<term>Perte d'audition (génétique)</term>
<term>Régulation de l'expression des gènes au cours du développement (MeSH)</term>
<term>Souris (MeSH)</term>
<term>Spécificité d'espèce (MeSH)</term>
<term>Stéréocils (métabolisme)</term>
<term>Séquence d'acides aminés (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Glutaredoxins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Perte d'audition</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Glutarédoxines</term>
</keywords>
<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Cochlée</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cochlée</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Cochlea</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Loci</term>
<term>Glutaredoxins</term>
<term>Hearing Loss</term>
</keywords>
<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Cochlea</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glutarédoxines</term>
<term>Locus génétiques</term>
<term>Perte d'audition</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glutaredoxins</term>
<term>Stereocilia</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glutarédoxines</term>
<term>Stéréocils</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Hearing Loss</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Gene Expression Regulation, Developmental</term>
<term>Humans</term>
<term>Mechanotransduction, Cellular</term>
<term>Mice</term>
<term>Models, Molecular</term>
<term>Morphogenesis</term>
<term>Mutation</term>
<term>Protein Conformation</term>
<term>Species Specificity</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Conformation des protéines</term>
<term>Humains</term>
<term>Modèles moléculaires</term>
<term>Morphogenèse</term>
<term>Mutation</term>
<term>Mécanotransduction cellulaire</term>
<term>Régulation de l'expression des gènes au cours du développement</term>
<term>Souris</term>
<term>Spécificité d'espèce</term>
<term>Séquence d'acides aminés</term>
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<front><div type="abstract" xml:lang="en">Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dimensions during development. In this study, we analyzed expression of the paralog Grxcr2 in the mouse and evaluated auditory and vestibular function of strains carrying targeted mutations of the gene. Peak expression of Grxcr2 occurs during early postnatal development of the inner ear and GRXCR2 is localized to stereocilia in both the cochlea and in vestibular organs. Homozygous Grxcr2 deletion mutants exhibit significant hearing loss by 3 weeks of age that is associated with developmental defects in stereocilia bundle orientation and organization. Despite these bundle defects, the mechanotransduction apparatus assembles in relatively normal fashion as determined by whole cell electrophysiological evaluation and FM1-43 uptake. Although Grxcr2 mutants do not exhibit overt vestibular dysfunction, evaluation of vestibular evoked potentials revealed subtle defects of the mutants in response to linear accelerations. In addition, reduced Grxcr2 expression in a hypomorphic mutant strain is associated with progressive hearing loss and bundle defects. The stereocilia localization of GRXCR2, together with the bundle pathologies observed in the mutants, indicate that GRXCR2 plays an intrinsic role in bundle orientation, organization, and sensory function in the inner ear during development and at maturity.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30157177</PMID>
<DateCompleted><Year>2019</Year>
<Month>02</Month>
<Day>04</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>02</Month>
<Day>15</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>13</Volume>
<Issue>8</Issue>
<PubDate><Year>2018</Year>
</PubDate>
</JournalIssue>
<Title>PloS one</Title>
<ISOAbbreviation>PLoS One</ISOAbbreviation>
</Journal>
<ArticleTitle>Grxcr2 is required for stereocilia morphogenesis in the cochlea.</ArticleTitle>
<Pagination><MedlinePgn>e0201713</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0201713</ELocationID>
<Abstract><AbstractText>Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dimensions during development. In this study, we analyzed expression of the paralog Grxcr2 in the mouse and evaluated auditory and vestibular function of strains carrying targeted mutations of the gene. Peak expression of Grxcr2 occurs during early postnatal development of the inner ear and GRXCR2 is localized to stereocilia in both the cochlea and in vestibular organs. Homozygous Grxcr2 deletion mutants exhibit significant hearing loss by 3 weeks of age that is associated with developmental defects in stereocilia bundle orientation and organization. Despite these bundle defects, the mechanotransduction apparatus assembles in relatively normal fashion as determined by whole cell electrophysiological evaluation and FM1-43 uptake. Although Grxcr2 mutants do not exhibit overt vestibular dysfunction, evaluation of vestibular evoked potentials revealed subtle defects of the mutants in response to linear accelerations. In addition, reduced Grxcr2 expression in a hypomorphic mutant strain is associated with progressive hearing loss and bundle defects. The stereocilia localization of GRXCR2, together with the bundle pathologies observed in the mutants, indicate that GRXCR2 plays an intrinsic role in bundle orientation, organization, and sensory function in the inner ear during development and at maturity.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Avenarius</LastName>
<ForeName>Matthew R</ForeName>
<Initials>MR</Initials>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jung</LastName>
<ForeName>Jae-Yun</ForeName>
<Initials>JY</Initials>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Askew</LastName>
<ForeName>Charles</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jones</LastName>
<ForeName>Sherri M</ForeName>
<Initials>SM</Initials>
<AffiliationInfo><Affiliation>Department of Communication Sciences and Disorders, East Carolina University, Greenville, North Carolina, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hunker</LastName>
<ForeName>Kristina L</ForeName>
<Initials>KL</Initials>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Azaiez</LastName>
<ForeName>Hela</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rehman</LastName>
<ForeName>Atteeq U</ForeName>
<Initials>AU</Initials>
<AffiliationInfo><Affiliation>Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schraders</LastName>
<ForeName>Margit</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Najmabadi</LastName>
<ForeName>Hossein</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kremer</LastName>
<ForeName>Hannie</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Smith</LastName>
<ForeName>Richard J H</ForeName>
<Initials>RJH</Initials>
<AffiliationInfo><Affiliation>Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Géléoc</LastName>
<ForeName>Gwenaëlle S G</ForeName>
<Initials>GSG</Initials>
<AffiliationInfo><Affiliation>Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dolan</LastName>
<ForeName>David F</ForeName>
<Initials>DF</Initials>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Raphael</LastName>
<ForeName>Yehoash</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kohrman</LastName>
<ForeName>David C</ForeName>
<Initials>DC</Initials>
<Identifier Source="ORCID">0000-0001-6888-6889</Identifier>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<DataBankList CompleteYN="Y"><DataBank><DataBankName>figshare</DataBankName>
<AccessionNumberList><AccessionNumber>10.6084/m9.figshare.c.4179050</AccessionNumber>
</AccessionNumberList>
</DataBank>
</DataBankList>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 DC006443</GrantID>
<Acronym>DC</Acronym>
<Agency>NIDCD NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DC008853</GrantID>
<Acronym>DC</Acronym>
<Agency>NIDCD NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 DC005188</GrantID>
<Acronym>DC</Acronym>
<Agency>NIDCD NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DC002842</GrantID>
<Acronym>DC</Acronym>
<Agency>NIDCD NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>T32 DC000011</GrantID>
<Acronym>DC</Acronym>
<Agency>NIDCD NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DC003049</GrantID>
<Acronym>DC</Acronym>
<Agency>NIDCD NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2018</Year>
<Month>08</Month>
<Day>29</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>PLoS One</MedlineTA>
<NlmUniqueID>101285081</NlmUniqueID>
<ISSNLinking>1932-6203</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C000593489">GRXCR2 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003051" MajorTopicYN="N">Cochlea</DescriptorName>
<QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName>
<QualifierName UI="Q000254" MajorTopicYN="Y">growth & development</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018507" MajorTopicYN="N">Gene Expression Regulation, Developmental</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D056426" MajorTopicYN="N">Genetic Loci</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D034381" MajorTopicYN="N">Hearing Loss</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D040542" MajorTopicYN="N">Mechanotransduction, Cellular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009024" MajorTopicYN="Y">Morphogenesis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011487" MajorTopicYN="N">Protein Conformation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013045" MajorTopicYN="N">Species Specificity</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059547" MajorTopicYN="N">Stereocilia</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<CoiStatement>The authors have declared that no competing interests exist.</CoiStatement>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year>
<Month>05</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2018</Year>
<Month>07</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2018</Year>
<Month>8</Month>
<Day>30</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2018</Year>
<Month>8</Month>
<Day>30</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2019</Year>
<Month>2</Month>
<Day>5</Day>
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Grxcr2 is required for stereocilia morphogenesis in the cochlea.

Grxcr2 is required for stereocilia morphogenesis in the cochlea.

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