SLC26A4 Targeted to the Endolymphatic Sac Rescues Hearing and Balance in Slc26a4 Mutant Mice
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{"title"=>"SLC26A4 Targeted to the Endolymphatic Sac Rescues Hearing and Balance in Slc26a4 Mutant Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Xiangming", "last_name"=>"Li", "scopus_author_id"=>"35319915300"}, {"first_name"=>"Joel D.", "last_name"=>"Sanneman", "scopus_author_id"=>"8625111800"}, {"first_name"=>"Donald G.", "last_name"=>"Harbidge", "scopus_author_id"=>"8625111900"}, {"first_name"=>"Fei", "last_name"=>"Zhou", "scopus_author_id"=>"55756034700"}, {"first_name"=>"Taku", "last_name"=>"Ito", "scopus_author_id"=>"55471040100"}, {"first_name"=>"Raoul", "last_name"=>"Nelson", "scopus_author_id"=>"7404561047"}, {"first_name"=>"Nicolas", "last_name"=>"Picard", "scopus_author_id"=>"35243242500"}, {"first_name"=>"Régine", "last_name"=>"Chambrey", "scopus_author_id"=>"6603744601"}, {"first_name"=>"Dominique", "last_name"=>"Eladari", "scopus_author_id"=>"6601980503"}, {"first_name"=>"Tracy", "last_name"=>"Miesner", "scopus_author_id"=>"28167728600"}, {"first_name"=>"Andrew J.", "last_name"=>"Griffith", "scopus_author_id"=>"7006238207"}, {"first_name"=>"Daniel C.", "last_name"=>"Marcus", "scopus_author_id"=>"7201798254"}, {"first_name"=>"Philine", "last_name"=>"Wangemann", "scopus_author_id"=>"54917710400"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-84880778696", "pui"=>"369438620", "doi"=>"10.1371/journal.pgen.1003641", "isbn"=>"1553-7404 (Electronic)\\n1553-7390 (Linking)", "sgr"=>"84880778696", "pmid"=>"23874234"}, "id"=>"d6cf7a1d-e9e0-36f7-9f6f-a95e2972863a", "abstract"=>"Mutations of SLC26A4 are a common cause of human hearing loss associated with enlargement of the vestibular aqueduct. SLC26A4 encodes pendrin, an anion exchanger expressed in a variety of epithelial cells in the cochlea, the vestibular labyrinth and the endolymphatic sac. Slc26a4 (Δ/Δ) mice are devoid of pendrin and develop a severe enlargement of the membranous labyrinth, fail to acquire hearing and balance, and thereby provide a model for the human phenotype. Here, we generated a transgenic mouse line that expresses human SLC26A4 controlled by the promoter of ATP6V1B1. Crossing this transgene into the Slc26a4 (Δ/Δ) line restored protein expression of pendrin in the endolymphatic sac without inducing detectable expression in the cochlea or the vestibular sensory organs. The transgene prevented abnormal enlargement of the membranous labyrinth, restored a normal endocochlear potential, normal pH gradients between endolymph and perilymph in the cochlea, normal otoconia formation in the vestibular labyrinth and normal sensory functions of hearing and balance. Our study demonstrates that restoration of pendrin to the endolymphatic sac is sufficient to restore normal inner ear function. This finding in conjunction with our previous report that pendrin expression is required for embryonic development but not for the maintenance of hearing opens the prospect that a spatially and temporally limited therapy will restore normal hearing in human patients carrying a variety of mutations of SLC26A4.", "link"=>"http://www.mendeley.com/research/slc26a4-targeted-endolymphatic-sac-rescues-hearing-balance-slc26a4-mutant-mice", "reader_count"=>17, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1117130"], "description"=>"<p>Endocochlear potential (<b>A</b>) and the difference between endolymphatic and perilymphatic pH (<b>B</b>) were measured in Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup>, Tg(+);<i>Slc26a4</i><sup>Δ/+</sup>, and Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice. Numbers near the error bars represent the number of experiments.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders"], "article_id"=>744192, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g008", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Endocochlear_potential_and_pH_/744192", "title"=>"Endocochlear potential and pH.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117139"], "description"=>"<p><b>A–C</b>) Microdissected maculae utriculi from a Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup>, Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice. The macula utriculi have been marked (<i>red dashed line</i>) and a single otoconium is indicated (<i>red arrow head</i>). <b>D–F</b>) Isolated otoconia from Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup>, Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice. Note that images <b>D</b>, <b>E.1</b>, <b>E.2</b>, <b>F.1</b> and <b>F.2</b> are presented at the same scale. Mega-otoconia were found only in Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup> mice. Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice contained a mixture of larger and smaller otoconia, some of which showed a concentric pattern (<b>E.1</b>, <b>E.2</b> and <b>E.3</b>) that was similar to the mixture found in Tg(−);<i>Slc26a4</i><sup>Δ/+</sup> mice (<b>F.1</b>, <b>F.2</b> and <b>F.3</b>).</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders"], "article_id"=>744200, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g011", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Otoconia_/744200", "title"=>"Otoconia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117118"], "description"=>"<p>Proteins in crude membranes prepared from pooled inner ear tissues consisting of soft tissues from the cochlea and the vestibular labyrinth devoid of endolymphatic sac and crude membranes prepared from kidneys of Tg(−)<i>Slc26a4</i><sup>Δ/+</sup>, Tg(−)<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+)<i>Slc26a4</i><sup>Δ/Δ</sup> mice were resolved by gel-electrophoresis and detected with an anti-pendrin antibody (Pds #1) and an anti-β-actin antibody. β-actin served as a loading control. <b>A</b>) Comparison of pendrin expression in membranes prepared from inner ears of Tg(−)<i>Slc26a4</i><sup>Δ/+</sup>, Tg(−)<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+)<i>Slc26a4</i><sup>Δ/Δ</sup> mice to expression levels in descending amounts of membranes prepared from kidneys of Tg(−)<i>Slc26a4</i><sup>Δ/+</sup> mice. <b>B</b>) Comparison of pendrin expression in membranes prepared from kidneys of Tg(−)<i>Slc26a4</i><sup>Δ/+</sup>, Tg(−)<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+)<i>Slc26a4</i><sup>Δ/Δ</sup> mice. <b>C</b>) Expression levels of pendrin in descending amounts of membranes prepared from kidneys of Tg(+)<i>Slc26a4</i><sup>Δ/Δ</sup> mice. Data shown in <b>A</b>, <b>B</b> and <b>C</b> are each representative of 2 biological replicates.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "evaluated"], "article_id"=>744180, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pendrin_expression_evaluated_by_Western_blotting_/744180", "title"=>"Pendrin expression evaluated by Western blotting.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117145", "https://ndownloader.figshare.com/files/1117146"], "description"=>"<div><p>Mutations of <i>SLC26A4</i> are a common cause of human hearing loss associated with enlargement of the vestibular aqueduct. <i>SLC26A4</i> encodes pendrin, an anion exchanger expressed in a variety of epithelial cells in the cochlea, the vestibular labyrinth and the endolymphatic sac. <i>Slc26a4</i><sup>Δ/Δ</sup> mice are devoid of pendrin and develop a severe enlargement of the membranous labyrinth, fail to acquire hearing and balance, and thereby provide a model for the human phenotype. Here, we generated a transgenic mouse line that expresses human <i>SLC26A4</i> controlled by the promoter of <i>ATP6V1B1</i>. Crossing this transgene into the <i>Slc26a4</i><sup>Δ/Δ</sup> line restored protein expression of pendrin in the endolymphatic sac without inducing detectable expression in the cochlea or the vestibular sensory organs. The transgene prevented abnormal enlargement of the membranous labyrinth, restored a normal endocochlear potential, normal pH gradients between endolymph and perilymph in the cochlea, normal otoconia formation in the vestibular labyrinth and normal sensory functions of hearing and balance. Our study demonstrates that restoration of pendrin to the endolymphatic sac is sufficient to restore normal inner ear function. This finding in conjunction with our previous report that pendrin expression is required for embryonic development but not for the maintenance of hearing opens the prospect that a spatially and temporally limited therapy will restore normal hearing in human patients carrying a variety of mutations of <i>SLC26A4</i>.</p></div>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "slc26a4", "targeted", "endolymphatic", "sac", "rescues", "mutant", "mice"], "article_id"=>744206, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003641.s001", "https://dx.doi.org/10.1371/journal.pgen.1003641.s002"], "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/SLC26A4_Targeted_to_the_Endolymphatic_Sac_Rescues_Hearing_and_Balance_in_Slc26a4_Mutant_Mice/744206", "title"=>"SLC26A4 Targeted to the Endolymphatic Sac Rescues Hearing and Balance in <i>Slc26a4</i> Mutant Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117113"], "description"=>"<p>Expression was determined by quantitative RT-PCR performed on total RNA. Total RNA was isolated from microdissected tissues obtained from Tg(−);<i>Slc26a4</i><sup>Δ/+</sup> (<b>A–D</b>) and Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice (<b>E–H</b>). Endolymphatic sacs (ES) were isolated from mice at age E17.5. Cochleae were isolated at ages E17.5 (C1) and P2 (C2). Vestibular labyrinths (VL), consisted of saccule, utricle, ampullae and semicircular canals without endolymphatic sacs, were isolated at age P8. The expression of endogenous mouse <i>Atp1a1</i>, <i>Atp6v1b1</i>, and <i>Slc26a4</i>, and of transgenic human <i>SLC26A4</i> mRNA was normalized to the expression of 18S rRNA. Note that the expression pattern of human <i>SLC26A4</i> in Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice resembles the pattern of mouse <i>Slc26a4</i> in Tg(−);<i>Slc26a4</i><sup>Δ/+</sup> mice (both patterns <i>highlighted in red</i>). Numbers inside graphs represent the number of experiments.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "mrna"], "article_id"=>744175, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Atp1a1_Atp6v1b1_Slc26a4_and_SLC26A4_mRNA_levels_in_inner_ear_tissues_/744175", "title"=>"<i>Atp1a1</i>, <i>Atp6v1b1</i>, <i>Slc26a4</i>, and <i>SLC26A4</i> mRNA levels in inner ear tissues.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117127"], "description"=>"<p><b>A–C</b>) Overview images of cochleae from a Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup>, Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice. The width of the lower cochlear turn is marked with arrows and the round (RW) and oval window (OW) are labeled. A region with apparently thinner bone is marked (*). <b>D–F</b>) Enlarged view of the oval window. Normal otoconia in the saccule that reflect the light and appear bright white were seen in Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice but not in Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup> (<i>arrow</i>). The number of mice represented by these images is 1 for <b>A</b> and <b>D</b>, and 3 pairs for images <b>B</b> & <b>C</b> and <b>E</b> & <b>F</b>.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "morphology", "cochlea"], "article_id"=>744189, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g006", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gross_morphology_of_the_cochlea_isolated_by_microdissection_/744189", "title"=>"Gross morphology of the cochlea isolated by microdissection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117112"], "description"=>"<p><b>A</b>) Diagram of the membranous labyrinth. The two continuous luminal fluid spaces of the mature inner ear are filled with endolymph (<i>pink</i> and <i>purple</i>). <b>B–E</b>) Diagrams of a cross section of one cochlear turn (<b>B</b>), of the utricle or saccule (<b>C</b>), of one ampulla (<b>D</b>) and the endolymphatic sac (<b>E</b>). Cells that express pendrin (<i>yellow cells</i> pointed to by <i>arrows</i>) are diagrammed in mature tissues.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "diagram"], "article_id"=>744174, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_diagram_of_the_inner_ear_/744174", "title"=>"Schematic diagram of the inner ear.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117123"], "description"=>"<p><b>A–B</b>) Paint filled inner ears from Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> and Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice at age E15.5. Note that neither the endolymphatic duct (E. duct) nor the endolymphatic sac (E. sac) were enlarged. <b>C–E</b>) Pendrin protein expression in the endolymphatic sac at age E16.5. Staining consisted of immunocytochemistry of pendrin (<i>red</i>) and F-actin (<i>green</i>). Images provide comparison of whole mounts from Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice (<b>C</b>), Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice (<b>D</b>), and Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup> mice (<b>E</b>). Note that images <b>C–E</b> are presented at the same scale. The number of mice represented by these images is 2 for <b>A</b>, 2 for <b>B</b>, 3 for <b>C</b>, 4 for <b>D</b>, and 1 for <b>E</b>. MR, mitochondria-rich cells.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "pendrin", "embryonic", "endolymphatic"], "article_id"=>744185, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g005", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histology_and_pendrin_expression_in_the_embryonic_endolymphatic_sac_/744185", "title"=>"Histology and pendrin expression in the embryonic endolymphatic sac.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117141"], "description"=>"<p>Tests were based on the ability of Tg(+);<i>Slc26a4</i><sup>Δ/+</sup>, Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup>, Tg(−);<i>Slc26a4</i><sup>Δ/+</sup>, Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup> mice to balance on a rotating rod that was accelerated from 4 to 40 rpm over 60 s. Numbers near the symbols indicate the number of mice evaluated.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders"], "article_id"=>744202, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g012", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Balance_tests_/744202", "title"=>"Balance tests.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117117"], "description"=>"<p><b>A–C</b>) Expression of eGFP was monitored as direct fluorescence in cochlear ducts (<b>A</b>), endolymphatic sacs (<b>B</b>), and kidney slices (<b>C</b>) freshly isolated from E15.5 Tg(<i>B1-eGFP</i>) mice. The outline of the imaged tissues is marked (<i>dashed-line</i>). <b>D–I</b>) Expression of eGFP was evaluated by immunocytochemistry in the cochlea (<b>D</b>), utricle (<b>E</b>), ampulla (<b>F</b>), endolymphatic sac (<b>G</b>), kidney cortex (<b>H</b>), and kidney medulla (<b>I</b>) from E15.5 Tg(<i>B1-eGFP</i>) mice. Staining consisted of immunocytochemistry of eGFP (<i>green</i>), F-actin (<i>red</i>) and nucleic acids (<i>blue</i>). The number of mice represented by these images are 2 for images <b>A–C</b> and 2 for images <b>D–I</b>. MR, mitochondria-rich cells; IC, intercalated cells; Lim, spiral limbus; K, Kölliker's organ; OS, outer sulcus; SV, stria vascularis; HC, vestibular hair cells; TC, transitional cells; M, melanocytes.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "egfp"], "article_id"=>744179, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transgene_encoded_eGFP_expression_/744179", "title"=>"Transgene-encoded eGFP expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117135"], "description"=>"<p>Staining in all images consisted of immunocytochemistry of pendrin (Pds #1 antibody; <i>red</i>) and F-actin (<i>green</i>) and of nucleic acids (<i>blue</i>), the latter with the exception of images <b>B</b> and <b>F</b>. Images provide comparison of cryosections (<b>A, C–D</b>) and whole-mounted specimens (<b>B</b>) from Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> to cryosections (<b>E, G–H</b>) and whole-mounted specimens (<b>F</b>) from Tg(−);<i>Slc26a4</i><sup>Δ/+</sup> mice. Whole-mounted specimens were imaged by detecting fluorescence in 25 optical sections that were recorded in 1 µm intervals and projected into a single plane. The number of pairs of mice represented by these images are 2 for image <b>A</b> & <b>E</b>, 1 for <b>B</b> & <b>F</b>, 2 for <b>C</b> & <b>G</b>, and 2 for <b>D</b> & <b>H</b> with 3 sections being evaluated per animal. HC, vestibular hair cells; TC, transitional cells; M, melanocytes. Additional images using an alternative anti-pendrin antibody (Pds #2) and alternative positive controls (Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice) are provided in the Supplement (<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003641#pgen.1003641.s002\" target=\"_blank\">Fig. S2</a>).</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "pendrin", "vestibular"], "article_id"=>744196, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g010", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histology_and_pendrin_expression_in_the_vestibular_labyrinth_/744196", "title"=>"Histology and pendrin expression in the vestibular labyrinth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117131"], "description"=>"<p><b>A–C</b>) Examples of recordings of auditory brain stem responses to tone bursts of 16 kHz at amplitudes between 0 and 90 dB-SPL that were presented to Tg(+);<i>Slc26a4</i><sup>+/+</sup> mice at P35 (<b>A</b>), Tg(−);<i>Slc26a4</i><sup>Δ/Δ</sup> mice at P35 (<b>B</b>), and Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice at P35 (<b>C</b>). Thresholds at 15 dB-SPL are marked (<i>thickened trace</i>). <b>D–L</b>) Hearing thresholds based on auditory brain stem responses, were determined in Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice (<b>D–F</b>), Tg(+);<i>Slc26a4</i><sup>+/+</sup> mice (<b>G–I</b>), and Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice (<b>J–L</b>; <i>highlighted in red</i>). Frequencies evaluated at 8 kHz (<b>D, G, J</b>), 16 kHz (<b>E, H, K</b>), and 32 kHz (<b>F, I, L</b>). The combined ranges of normal hearing in the three mouse strains (129S6, C57BL/6 and CBA) that contributed to the background of the mice are marked (<i>grey rectangles</i>). Numbers next to symbols in <b>D–L</b> represent the number of mice tested.</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "auditory"], "article_id"=>744193, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g009", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hearing_tests_based_on_auditory_brain_stem_responses_/744193", "title"=>"Hearing tests based on auditory brain stem responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1117129"], "description"=>"<p>Staining in all images consisted of immunocytochemistry of pendrin (Pds #1 antibody; <i>red</i>), F-actin (<i>green</i>) and nucleic acids (<i>blue</i>). Images provide comparison of cryosections (<b>A–B</b>) and whole-mounted specimens (<b>C–E</b>) from Tg(+);<i>Slc26a4</i><sup>Δ/Δ</sup> mice to cryosections (<b>F–G</b>) and whole-mounted specimens (<b>H–J</b>) from Tg(−);<i>Slc26a4</i><sup>Δ/+</sup> mice. Whole-mounted specimens in <b>C</b>, <b>E</b>, <b>H</b> and <b>J</b> were imaged by detecting fluorescence in 25 optical sections that were recorded in 1 µm intervals and projected into a single plane. Whole-mounted specimens in <b>D</b> and <b>I</b> were imaged by detecting fluorescence in 8 optical sections that were recorded in 1 µm intervals, projected into a single plane and overlaid onto a single brightfield image. The number of pairs of mice represented by these images are 2 for image <b>A</b> & <b>F</b>, 3 for <b>B</b> & <b>G</b>, and 1 for <b>C–E</b> & <b>H–J</b> with 3 sections being evaluated per animal. K, Kölliker's organ; OS, outer sulcus; Lim, spiral limbus; IS, inner sulcus; OC, organ of Corti; SP, spiral prominence; SV, stria vascularis; RM, Reissner's membrane. Additional images using an alternative anti-pendrin antibody (Pds #2) and alternative positive controls (Tg(+);<i>Slc26a4</i><sup>Δ/+</sup> mice) are provided in the Supplement (<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003641#pgen.1003641.s001\" target=\"_blank\">Fig. S1</a>).</p>", "links"=>[], "tags"=>["developmental biology", "morphogenesis", "genetics", "gene expression", "Gene function", "Genetic mutation", "Genetics of disease", "Molecular genetics", "otorhinolaryngology", "Otology", "Hearing disorders", "pendrin"], "article_id"=>744191, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Xiangming Li", "Joel D. Sanneman", "Donald G. Harbidge", "Fei Zhou", "Taku Ito", "Raoul Nelson", "Nicolas Picard", "Régine Chambrey", "Dominique Eladari", "Tracy Miesner", "Andrew J. Griffith", "Daniel C. Marcus", "Philine Wangemann"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003641.g007", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histology_and_pendrin_expression_in_the_cochlea_/744191", "title"=>"Histology and pendrin expression in the cochlea.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-11 02:28:57"}

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Relative Metric

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