Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice
Both the ahl allele of Cdh23 and the null mutation of Sod1 have been shown to contribute to age-related hearing loss (AHL) in mice, but mixed strain backgrounds have confounded analyses of their individual and combined effects. To test for the effects of Sod1 deficiency independently from those of C...
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| creator | Johnson, Kenneth R. Yu, Heping Ding, Dalian Jiang, Haiyan Gagnon, Leona H. Salvi, Richard J. |
| description | Both the
ahl allele of
Cdh23 and the null mutation of
Sod1 have been shown to contribute to age-related hearing loss (AHL) in mice, but mixed strain backgrounds have confounded analyses of their individual and combined effects. To test for the effects of
Sod1 deficiency independently from those of
Cdh23
ahl
, we produced mice with four digenic genotypes:
Sod1
+/+
Cdh23
ahl
/
ahl
,
Sod1
+/+
Cdh23
+/+,
Sod1
−/−
Cdh23
ahl
/
ahl
, and
Sod1
−/−
Cdh23
+/+, all on a uniform C57BL
/6J strain background. We assessed hearing loss by ABR threshold measurements and evaluated cochlear pathologies in age-matched mice of each digenic combination. ABR analysis showed that
Sod1
+/+
Cdh23
+/+ mice retain normal hearing up to 15 months of age and that hearing loss of
Sod1
+/+
Cdh23
ahl
/
ahl
mice is more age and frequency dependent than that of
Sod1
−/−
Cdh23
+/+ mice. ABR results also showed that mice with both gene mutations (
Sod1
−/−
Cdh23
ahl
/
ahl
) exhibit the earliest onset and most severe hearing loss, greater than predicted for strictly additive effects. Histological analysis of cochleas showed that hair cell lesions are most severe in
Sod1
−
/
−
Cdh23
ahl
/
ahl
mice followed closely by
Sod1
+
/
+
Cdh23
ahl
/
ahl
mice and much smaller in
Sod1
−
/
−
Cdh23
+
/
+
and
Sod1
+
/
+
Cdh23
+
/
+
mice. Despite extensive damage to cochlear hair cells, vestibular hair cells appeared remarkably normal in all strains. Although both
Sod1
−/− and
Cdh23
ahl
/
ahl
genotypes had strong effects on hearing loss, the
Cdh23
ahl/ahl
genotype was primarily responsible for the increase in hair cell loss, suggesting that the two mutations have different underlying mechanisms of pathology. |
| doi_str_mv | 10.1016/j.heares.2010.05.002 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2923272</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0378595510002479</els_id><sourcerecordid>817604657</sourcerecordid><originalsourceid>FETCH-LOGICAL-c590t-10afe8454bc515e571f4ea241293e0a5bfbea68e79c41889d0d6bc6242d46bb53</originalsourceid><addsrcrecordid>eNqFUU2P0zAUtBCILYV_gJAviFO6tmPHzgUJql0-VInDwtly7JfGVWIXO11pD_x3XFp24QInW2_mjebNIPSSkhUltLncrQYwCfKKkTIiYkUIe4QWVElVCdXSx2hB6uO_FeICPct5RwgVNWdP0QUjXBIl-QL9uIG9SWYGbILDNk6dD-Aw9D3YOePY45vo6C9w7QZW4-kwm9nHULCAzRaqBGNZd_joxoctHmPOZzE7jGWI92Ye4hi3d9gHvBby_eay-Ywnb-E5etKbMcOL87tE366vvq4_VpsvHz6t320qK1oyV5SYHhQXvLOCChCS9hwM45S1NRAjur4D0yiQreVUqdYR13S2YZw53nSdqJfo7Ul3f-gmcBbCnMyo98lPJt3paLz-Gwl-0Nt4q1nLaiZZEXhzFkjx-wHyrCefLYyjCRAPWSsqG8IbIf_LlFy1ijfF-RLxE9OmElmC_t4PJfpYsd7pU8X6WLEmQpeKy9qrP2-5X_rdaSG8PhNMtmbskwnW5wdeTaXgtXoIBUrytx6SztZDsOB8KuVrF_2_nfwEDATGxA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>748984629</pqid></control><display><type>article</type><title>Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Johnson, Kenneth R. ; Yu, Heping ; Ding, Dalian ; Jiang, Haiyan ; Gagnon, Leona H. ; Salvi, Richard J.</creator><creatorcontrib>Johnson, Kenneth R. ; Yu, Heping ; Ding, Dalian ; Jiang, Haiyan ; Gagnon, Leona H. ; Salvi, Richard J.</creatorcontrib><description>Both the
ahl allele of
Cdh23 and the null mutation of
Sod1 have been shown to contribute to age-related hearing loss (AHL) in mice, but mixed strain backgrounds have confounded analyses of their individual and combined effects. To test for the effects of
Sod1 deficiency independently from those of
Cdh23
ahl
, we produced mice with four digenic genotypes:
Sod1
+/+
Cdh23
ahl
/
ahl
,
Sod1
+/+
Cdh23
+/+,
Sod1
−/−
Cdh23
ahl
/
ahl
, and
Sod1
−/−
Cdh23
+/+, all on a uniform C57BL
/6J strain background. We assessed hearing loss by ABR threshold measurements and evaluated cochlear pathologies in age-matched mice of each digenic combination. ABR analysis showed that
Sod1
+/+
Cdh23
+/+ mice retain normal hearing up to 15 months of age and that hearing loss of
Sod1
+/+
Cdh23
ahl
/
ahl
mice is more age and frequency dependent than that of
Sod1
−/−
Cdh23
+/+ mice. ABR results also showed that mice with both gene mutations (
Sod1
−/−
Cdh23
ahl
/
ahl
) exhibit the earliest onset and most severe hearing loss, greater than predicted for strictly additive effects. Histological analysis of cochleas showed that hair cell lesions are most severe in
Sod1
−
/
−
Cdh23
ahl
/
ahl
mice followed closely by
Sod1
+
/
+
Cdh23
ahl
/
ahl
mice and much smaller in
Sod1
−
/
−
Cdh23
+
/
+
and
Sod1
+
/
+
Cdh23
+
/
+
mice. Despite extensive damage to cochlear hair cells, vestibular hair cells appeared remarkably normal in all strains. Although both
Sod1
−/− and
Cdh23
ahl
/
ahl
genotypes had strong effects on hearing loss, the
Cdh23
ahl/ahl
genotype was primarily responsible for the increase in hair cell loss, suggesting that the two mutations have different underlying mechanisms of pathology.</description><identifier>ISSN: 0378-5955</identifier><identifier>EISSN: 1878-5891</identifier><identifier>DOI: 10.1016/j.heares.2010.05.002</identifier><identifier>PMID: 20470874</identifier><identifier>CODEN: HERED3</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Acoustic Stimulation ; Age Factors ; Aging ; Animals ; Auditory Threshold ; Biological and medical sciences ; Cadherins - genetics ; Cadherins - metabolism ; Chemical and industrial products toxicology. Toxic occupational diseases ; Cochlea - pathology ; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology ; Evoked Potentials, Auditory, Brain Stem ; Genetic Predisposition to Disease ; Hair Cells, Auditory - pathology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Non tumoral diseases ; Otorhinolaryngology. Stomatology ; Presbycusis - genetics ; Presbycusis - metabolism ; Presbycusis - pathology ; Severity of Illness Index ; Solvents ; Superoxide Dismutase - genetics ; Superoxide Dismutase - metabolism ; Superoxide Dismutase-1 ; Toxicology</subject><ispartof>Hearing research, 2010-09, Vol.268 (1), p.85-92</ispartof><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-10afe8454bc515e571f4ea241293e0a5bfbea68e79c41889d0d6bc6242d46bb53</citedby><cites>FETCH-LOGICAL-c590t-10afe8454bc515e571f4ea241293e0a5bfbea68e79c41889d0d6bc6242d46bb53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.heares.2010.05.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23175438$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20470874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Johnson, Kenneth R.</creatorcontrib><creatorcontrib>Yu, Heping</creatorcontrib><creatorcontrib>Ding, Dalian</creatorcontrib><creatorcontrib>Jiang, Haiyan</creatorcontrib><creatorcontrib>Gagnon, Leona H.</creatorcontrib><creatorcontrib>Salvi, Richard J.</creatorcontrib><title>Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice</title><title>Hearing research</title><addtitle>Hear Res</addtitle><description>Both the
ahl allele of
Cdh23 and the null mutation of
Sod1 have been shown to contribute to age-related hearing loss (AHL) in mice, but mixed strain backgrounds have confounded analyses of their individual and combined effects. To test for the effects of
Sod1 deficiency independently from those of
Cdh23
ahl
, we produced mice with four digenic genotypes:
Sod1
+/+
Cdh23
ahl
/
ahl
,
Sod1
+/+
Cdh23
+/+,
Sod1
−/−
Cdh23
ahl
/
ahl
, and
Sod1
−/−
Cdh23
+/+, all on a uniform C57BL
/6J strain background. We assessed hearing loss by ABR threshold measurements and evaluated cochlear pathologies in age-matched mice of each digenic combination. ABR analysis showed that
Sod1
+/+
Cdh23
+/+ mice retain normal hearing up to 15 months of age and that hearing loss of
Sod1
+/+
Cdh23
ahl
/
ahl
mice is more age and frequency dependent than that of
Sod1
−/−
Cdh23
+/+ mice. ABR results also showed that mice with both gene mutations (
Sod1
−/−
Cdh23
ahl
/
ahl
) exhibit the earliest onset and most severe hearing loss, greater than predicted for strictly additive effects. Histological analysis of cochleas showed that hair cell lesions are most severe in
Sod1
−
/
−
Cdh23
ahl
/
ahl
mice followed closely by
Sod1
+
/
+
Cdh23
ahl
/
ahl
mice and much smaller in
Sod1
−
/
−
Cdh23
+
/
+
and
Sod1
+
/
+
Cdh23
+
/
+
mice. Despite extensive damage to cochlear hair cells, vestibular hair cells appeared remarkably normal in all strains. Although both
Sod1
−/− and
Cdh23
ahl
/
ahl
genotypes had strong effects on hearing loss, the
Cdh23
ahl/ahl
genotype was primarily responsible for the increase in hair cell loss, suggesting that the two mutations have different underlying mechanisms of pathology.</description><subject>Acoustic Stimulation</subject><subject>Age Factors</subject><subject>Aging</subject><subject>Animals</subject><subject>Auditory Threshold</subject><subject>Biological and medical sciences</subject><subject>Cadherins - genetics</subject><subject>Cadherins - metabolism</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>Cochlea - pathology</subject><subject>Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology</subject><subject>Evoked Potentials, Auditory, Brain Stem</subject><subject>Genetic Predisposition to Disease</subject><subject>Hair Cells, Auditory - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mutation</subject><subject>Non tumoral diseases</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Presbycusis - genetics</subject><subject>Presbycusis - metabolism</subject><subject>Presbycusis - pathology</subject><subject>Severity of Illness Index</subject><subject>Solvents</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Superoxide Dismutase-1</subject><subject>Toxicology</subject><issn>0378-5955</issn><issn>1878-5891</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU2P0zAUtBCILYV_gJAviFO6tmPHzgUJql0-VInDwtly7JfGVWIXO11pD_x3XFp24QInW2_mjebNIPSSkhUltLncrQYwCfKKkTIiYkUIe4QWVElVCdXSx2hB6uO_FeICPct5RwgVNWdP0QUjXBIl-QL9uIG9SWYGbILDNk6dD-Aw9D3YOePY45vo6C9w7QZW4-kwm9nHULCAzRaqBGNZd_joxoctHmPOZzE7jGWI92Ye4hi3d9gHvBby_eay-Ywnb-E5etKbMcOL87tE366vvq4_VpsvHz6t320qK1oyV5SYHhQXvLOCChCS9hwM45S1NRAjur4D0yiQreVUqdYR13S2YZw53nSdqJfo7Ul3f-gmcBbCnMyo98lPJt3paLz-Gwl-0Nt4q1nLaiZZEXhzFkjx-wHyrCefLYyjCRAPWSsqG8IbIf_LlFy1ijfF-RLxE9OmElmC_t4PJfpYsd7pU8X6WLEmQpeKy9qrP2-5X_rdaSG8PhNMtmbskwnW5wdeTaXgtXoIBUrytx6SztZDsOB8KuVrF_2_nfwEDATGxA</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>Johnson, Kenneth R.</creator><creator>Yu, Heping</creator><creator>Ding, Dalian</creator><creator>Jiang, Haiyan</creator><creator>Gagnon, Leona H.</creator><creator>Salvi, Richard J.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20100901</creationdate><title>Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice</title><author>Johnson, Kenneth R. ; Yu, Heping ; Ding, Dalian ; Jiang, Haiyan ; Gagnon, Leona H. ; Salvi, Richard J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c590t-10afe8454bc515e571f4ea241293e0a5bfbea68e79c41889d0d6bc6242d46bb53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acoustic Stimulation</topic><topic>Age Factors</topic><topic>Aging</topic><topic>Animals</topic><topic>Auditory Threshold</topic><topic>Biological and medical sciences</topic><topic>Cadherins - genetics</topic><topic>Cadherins - metabolism</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>Cochlea - pathology</topic><topic>Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology</topic><topic>Evoked Potentials, Auditory, Brain Stem</topic><topic>Genetic Predisposition to Disease</topic><topic>Hair Cells, Auditory - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mutation</topic><topic>Non tumoral diseases</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Presbycusis - genetics</topic><topic>Presbycusis - metabolism</topic><topic>Presbycusis - pathology</topic><topic>Severity of Illness Index</topic><topic>Solvents</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Superoxide Dismutase-1</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Johnson, Kenneth R.</creatorcontrib><creatorcontrib>Yu, Heping</creatorcontrib><creatorcontrib>Ding, Dalian</creatorcontrib><creatorcontrib>Jiang, Haiyan</creatorcontrib><creatorcontrib>Gagnon, Leona H.</creatorcontrib><creatorcontrib>Salvi, Richard J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Hearing research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Johnson, Kenneth R.</au><au>Yu, Heping</au><au>Ding, Dalian</au><au>Jiang, Haiyan</au><au>Gagnon, Leona H.</au><au>Salvi, Richard J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice</atitle><jtitle>Hearing research</jtitle><addtitle>Hear Res</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>268</volume><issue>1</issue><spage>85</spage><epage>92</epage><pages>85-92</pages><issn>0378-5955</issn><eissn>1878-5891</eissn><coden>HERED3</coden><abstract>Both the
ahl allele of
Cdh23 and the null mutation of
Sod1 have been shown to contribute to age-related hearing loss (AHL) in mice, but mixed strain backgrounds have confounded analyses of their individual and combined effects. To test for the effects of
Sod1 deficiency independently from those of
Cdh23
ahl
, we produced mice with four digenic genotypes:
Sod1
+/+
Cdh23
ahl
/
ahl
,
Sod1
+/+
Cdh23
+/+,
Sod1
−/−
Cdh23
ahl
/
ahl
, and
Sod1
−/−
Cdh23
+/+, all on a uniform C57BL
/6J strain background. We assessed hearing loss by ABR threshold measurements and evaluated cochlear pathologies in age-matched mice of each digenic combination. ABR analysis showed that
Sod1
+/+
Cdh23
+/+ mice retain normal hearing up to 15 months of age and that hearing loss of
Sod1
+/+
Cdh23
ahl
/
ahl
mice is more age and frequency dependent than that of
Sod1
−/−
Cdh23
+/+ mice. ABR results also showed that mice with both gene mutations (
Sod1
−/−
Cdh23
ahl
/
ahl
) exhibit the earliest onset and most severe hearing loss, greater than predicted for strictly additive effects. Histological analysis of cochleas showed that hair cell lesions are most severe in
Sod1
−
/
−
Cdh23
ahl
/
ahl
mice followed closely by
Sod1
+
/
+
Cdh23
ahl
/
ahl
mice and much smaller in
Sod1
−
/
−
Cdh23
+
/
+
and
Sod1
+
/
+
Cdh23
+
/
+
mice. Despite extensive damage to cochlear hair cells, vestibular hair cells appeared remarkably normal in all strains. Although both
Sod1
−/− and
Cdh23
ahl
/
ahl
genotypes had strong effects on hearing loss, the
Cdh23
ahl/ahl
genotype was primarily responsible for the increase in hair cell loss, suggesting that the two mutations have different underlying mechanisms of pathology.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>20470874</pmid><doi>10.1016/j.heares.2010.05.002</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0378-5955 |
| ispartof | Hearing research, 2010-09, Vol.268 (1), p.85-92 |
| issn | 0378-5955 1878-5891 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2923272 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Acoustic Stimulation Age Factors Aging Animals Auditory Threshold Biological and medical sciences Cadherins - genetics Cadherins - metabolism Chemical and industrial products toxicology. Toxic occupational diseases Cochlea - pathology Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology Evoked Potentials, Auditory, Brain Stem Genetic Predisposition to Disease Hair Cells, Auditory - pathology Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Mutation Non tumoral diseases Otorhinolaryngology. Stomatology Presbycusis - genetics Presbycusis - metabolism Presbycusis - pathology Severity of Illness Index Solvents Superoxide Dismutase - genetics Superoxide Dismutase - metabolism Superoxide Dismutase-1 Toxicology |
| title | Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice |
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