Auditory and vestibular defects in the circling (ci2) rat mutant
The circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behaviour, locomotor hyperactivity, ataxia and stereotypic head‐movement. These abnormal behaviours occur in phases or bursts either spontaneously or in response to stress. Heterozygous (ci2/+)...
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creator | Kaiser, Alexander Fedrowitz, Maren Ebert, Ulrich Zimmermann, Elke Hedrich, Hans-Jürgen Wedekind, Dirk Löscher, Wolfgang |
description | The circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behaviour, locomotor hyperactivity, ataxia and stereotypic head‐movement. These abnormal behaviours occur in phases or bursts either spontaneously or in response to stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviours. We have previously found that ci2/ci2 rats of both genders have a lower tissue content of dopamine in the striatum ipsilateral to the preferred direction of rotation, indicating that the rats turn away from the brain hemisphere with higher striatal dopaminergic activity. In view of the similarities of the motor syndrome of the ci2/ci2 mutant rat to that of mouse deafness mutants, the present study evaluated the hearing ability of the circling rat mutant by recording brainstem auditory‐evoked potentials. To test for vestibular dysfunction, a swimming test was conducted. Histological methods were used to examine the cochlear and vestibular parts of the inner ear and the cochlear and vestibular brainstem nuclei for defects. The absence of auditory‐evoked potentials demonstrated a complete hearing loss in the adult ci2/ci2 mutant rat, whereas heterozygous littermates exhibited auditory‐evoked potentials with thresholds resembling those of other laboratory strains. Furthermore, the mutant rats were unable to swim. Histological analysis of the inner ear of adult mutants revealed virtually complete loss of the cochlear neuroepithelium, while no such hair cell degeneration was seen in the vestibular parts of the inner ear. However, part of the vestibular hair cells showed protrusions into the endolymphatic space, suggesting alterations in the cytoskeletal architecture. The histological findings in mutant circling rats strongly indicate that the hearing loss of the mutants is of the sensory neural type, the most prevalent type of hearing loss. In the cochlear nuclei of the brain stem of mutant rats, neurons exhibited an abnormal shape, reduced size and increased density compared to controls. In contrast, no abnormal neuronal morphology was seen in the vestibular nuclei, but a significantly reduced neuronal density was found in the medial vestibular nucleus. Abnormal vestibular function would be a likely explanation for the disturbed balance of mutant rats as exemplified by the ataxia and the inability to swim, whereas the previous data on these rats strongly indicate an involvement of the basal ganglia in the abnormal ci |
doi_str_mv | 10.1046/j.0953-816x.2001.01726.x |
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These abnormal behaviours occur in phases or bursts either spontaneously or in response to stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviours. We have previously found that ci2/ci2 rats of both genders have a lower tissue content of dopamine in the striatum ipsilateral to the preferred direction of rotation, indicating that the rats turn away from the brain hemisphere with higher striatal dopaminergic activity. In view of the similarities of the motor syndrome of the ci2/ci2 mutant rat to that of mouse deafness mutants, the present study evaluated the hearing ability of the circling rat mutant by recording brainstem auditory‐evoked potentials. To test for vestibular dysfunction, a swimming test was conducted. Histological methods were used to examine the cochlear and vestibular parts of the inner ear and the cochlear and vestibular brainstem nuclei for defects. The absence of auditory‐evoked potentials demonstrated a complete hearing loss in the adult ci2/ci2 mutant rat, whereas heterozygous littermates exhibited auditory‐evoked potentials with thresholds resembling those of other laboratory strains. Furthermore, the mutant rats were unable to swim. Histological analysis of the inner ear of adult mutants revealed virtually complete loss of the cochlear neuroepithelium, while no such hair cell degeneration was seen in the vestibular parts of the inner ear. However, part of the vestibular hair cells showed protrusions into the endolymphatic space, suggesting alterations in the cytoskeletal architecture. The histological findings in mutant circling rats strongly indicate that the hearing loss of the mutants is of the sensory neural type, the most prevalent type of hearing loss. In the cochlear nuclei of the brain stem of mutant rats, neurons exhibited an abnormal shape, reduced size and increased density compared to controls. In contrast, no abnormal neuronal morphology was seen in the vestibular nuclei, but a significantly reduced neuronal density was found in the medial vestibular nucleus. Abnormal vestibular function would be a likely explanation for the disturbed balance of mutant rats as exemplified by the ataxia and the inability to swim, whereas the previous data on these rats strongly indicate an involvement of the basal ganglia in the abnormal circling behaviour. The genetic defect in the mutant rats, thus, results in a clinical syndrome with features also seen in human genetic disorders with deafness and hyperkinesia, making the ci2/ci2 rat an excellent model for investigating both cochlear/vestibular dysfunction and hyperkinetic movement disorders.</description><identifier>ISSN: 0953-816X</identifier><identifier>EISSN: 1460-9568</identifier><identifier>DOI: 10.1046/j.0953-816x.2001.01726.x</identifier><identifier>PMID: 11683905</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Animals ; cochlea ; Cochlea - abnormalities ; Cochlea - pathology ; Cochlea - physiopathology ; cochlear nuclei ; Cochlear Nucleus - abnormalities ; Cochlear Nucleus - pathology ; Cochlear Nucleus - physiopathology ; Deafness - pathology ; Deafness - physiopathology ; Disease Models, Animal ; dopamine ; Evoked Potentials, Auditory - genetics ; Female ; hearing loss ; Male ; Rats ; Rats, Mutant Strains - abnormalities ; Rats, Mutant Strains - metabolism ; rotational behaviour ; Space life sciences ; Swimming - physiology ; Tabes Dorsalis - congenital ; Tabes Dorsalis - pathology ; Tabes Dorsalis - physiopathology ; Vestibular Diseases - pathology ; Vestibular Diseases - physiopathology ; Vestibular Function Tests ; Vestibular Nuclei - abnormalities ; Vestibular Nuclei - pathology ; Vestibular Nuclei - physiopathology ; Vestibule, Labyrinth - abnormalities ; Vestibule, Labyrinth - pathology ; Vestibule, Labyrinth - physiopathology</subject><ispartof>The European journal of neuroscience, 2001-10, Vol.14 (7), p.1129-1142</ispartof><rights>Federation of European Neuroscience Societies</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5026-ef3e5194ebb1bf0df612fbe7a599e433f7e58cae74f22f156655f659088bcfe73</citedby><cites>FETCH-LOGICAL-c5026-ef3e5194ebb1bf0df612fbe7a599e433f7e58cae74f22f156655f659088bcfe73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.0953-816x.2001.01726.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.0953-816x.2001.01726.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11683905$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaiser, Alexander</creatorcontrib><creatorcontrib>Fedrowitz, Maren</creatorcontrib><creatorcontrib>Ebert, Ulrich</creatorcontrib><creatorcontrib>Zimmermann, Elke</creatorcontrib><creatorcontrib>Hedrich, Hans-Jürgen</creatorcontrib><creatorcontrib>Wedekind, Dirk</creatorcontrib><creatorcontrib>Löscher, Wolfgang</creatorcontrib><title>Auditory and vestibular defects in the circling (ci2) rat mutant</title><title>The European journal of neuroscience</title><addtitle>Eur J Neurosci</addtitle><description>The circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behaviour, locomotor hyperactivity, ataxia and stereotypic head‐movement. These abnormal behaviours occur in phases or bursts either spontaneously or in response to stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviours. We have previously found that ci2/ci2 rats of both genders have a lower tissue content of dopamine in the striatum ipsilateral to the preferred direction of rotation, indicating that the rats turn away from the brain hemisphere with higher striatal dopaminergic activity. In view of the similarities of the motor syndrome of the ci2/ci2 mutant rat to that of mouse deafness mutants, the present study evaluated the hearing ability of the circling rat mutant by recording brainstem auditory‐evoked potentials. To test for vestibular dysfunction, a swimming test was conducted. Histological methods were used to examine the cochlear and vestibular parts of the inner ear and the cochlear and vestibular brainstem nuclei for defects. The absence of auditory‐evoked potentials demonstrated a complete hearing loss in the adult ci2/ci2 mutant rat, whereas heterozygous littermates exhibited auditory‐evoked potentials with thresholds resembling those of other laboratory strains. Furthermore, the mutant rats were unable to swim. Histological analysis of the inner ear of adult mutants revealed virtually complete loss of the cochlear neuroepithelium, while no such hair cell degeneration was seen in the vestibular parts of the inner ear. However, part of the vestibular hair cells showed protrusions into the endolymphatic space, suggesting alterations in the cytoskeletal architecture. The histological findings in mutant circling rats strongly indicate that the hearing loss of the mutants is of the sensory neural type, the most prevalent type of hearing loss. In the cochlear nuclei of the brain stem of mutant rats, neurons exhibited an abnormal shape, reduced size and increased density compared to controls. In contrast, no abnormal neuronal morphology was seen in the vestibular nuclei, but a significantly reduced neuronal density was found in the medial vestibular nucleus. Abnormal vestibular function would be a likely explanation for the disturbed balance of mutant rats as exemplified by the ataxia and the inability to swim, whereas the previous data on these rats strongly indicate an involvement of the basal ganglia in the abnormal circling behaviour. The genetic defect in the mutant rats, thus, results in a clinical syndrome with features also seen in human genetic disorders with deafness and hyperkinesia, making the ci2/ci2 rat an excellent model for investigating both cochlear/vestibular dysfunction and hyperkinetic movement disorders.</description><subject>Animals</subject><subject>cochlea</subject><subject>Cochlea - abnormalities</subject><subject>Cochlea - pathology</subject><subject>Cochlea - physiopathology</subject><subject>cochlear nuclei</subject><subject>Cochlear Nucleus - abnormalities</subject><subject>Cochlear Nucleus - pathology</subject><subject>Cochlear Nucleus - physiopathology</subject><subject>Deafness - pathology</subject><subject>Deafness - physiopathology</subject><subject>Disease Models, Animal</subject><subject>dopamine</subject><subject>Evoked Potentials, Auditory - genetics</subject><subject>Female</subject><subject>hearing loss</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Mutant Strains - abnormalities</subject><subject>Rats, Mutant Strains - metabolism</subject><subject>rotational behaviour</subject><subject>Space life sciences</subject><subject>Swimming - physiology</subject><subject>Tabes Dorsalis - congenital</subject><subject>Tabes Dorsalis - pathology</subject><subject>Tabes Dorsalis - physiopathology</subject><subject>Vestibular Diseases - pathology</subject><subject>Vestibular Diseases - physiopathology</subject><subject>Vestibular Function Tests</subject><subject>Vestibular Nuclei - abnormalities</subject><subject>Vestibular Nuclei - pathology</subject><subject>Vestibular Nuclei - physiopathology</subject><subject>Vestibule, Labyrinth - abnormalities</subject><subject>Vestibule, Labyrinth - pathology</subject><subject>Vestibule, Labyrinth - physiopathology</subject><issn>0953-816X</issn><issn>1460-9568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtu1DAUQK0KRIfCL1ReobJI8CN-LZBoq9KCRgVVoCI2luNctx4ymWInMPP3JMzQ7lBXvotz7rUOQpiSkpJKvlmUxAheaCrXJSOEloQqJsv1HprRSpLCCKmfoNk_6Ns-ep7zghCiZSWeoX1KpeaGiBl6dzw0sV-lDXZdg39B7mM9tC7hBgL4PuPY4f4WsI_Jt7G7wUc-stc4uR4vh951_Qv0NLg2w8vde4C-vj_7cnpRzD-dfzg9nhdeECYLCBwENRXUNa0DaYKkLNSgnDAGKs6DAqG9A1UFxgIVUgoRpDBE69oHUPwAvdruvUurn8P4T7uM2UPbug5WQ7aKMS6N4SN49F-Q6rGClKQSI6q3qE-rnBMEe5fi0qWNpcROoe3CTg3tFNpOoe3f0HY9qoe7K0O9hOZB3JUdgbdb4HdsYfPoxfbs4-U0jX6x9WPuYX3vu_TDSsWVsNeX53Z-oT5fnXxX9or_AUIkmzU</recordid><startdate>200110</startdate><enddate>200110</enddate><creator>Kaiser, Alexander</creator><creator>Fedrowitz, Maren</creator><creator>Ebert, Ulrich</creator><creator>Zimmermann, Elke</creator><creator>Hedrich, Hans-Jürgen</creator><creator>Wedekind, Dirk</creator><creator>Löscher, Wolfgang</creator><general>Blackwell Science Ltd</general><scope>BSCLL</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>200110</creationdate><title>Auditory and vestibular defects in the circling (ci2) rat mutant</title><author>Kaiser, Alexander ; Fedrowitz, Maren ; Ebert, Ulrich ; Zimmermann, Elke ; Hedrich, Hans-Jürgen ; Wedekind, Dirk ; Löscher, Wolfgang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5026-ef3e5194ebb1bf0df612fbe7a599e433f7e58cae74f22f156655f659088bcfe73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>cochlea</topic><topic>Cochlea - abnormalities</topic><topic>Cochlea - pathology</topic><topic>Cochlea - physiopathology</topic><topic>cochlear nuclei</topic><topic>Cochlear Nucleus - abnormalities</topic><topic>Cochlear Nucleus - pathology</topic><topic>Cochlear Nucleus - physiopathology</topic><topic>Deafness - pathology</topic><topic>Deafness - physiopathology</topic><topic>Disease Models, Animal</topic><topic>dopamine</topic><topic>Evoked Potentials, Auditory - genetics</topic><topic>Female</topic><topic>hearing loss</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Mutant Strains - abnormalities</topic><topic>Rats, Mutant Strains - metabolism</topic><topic>rotational behaviour</topic><topic>Space life sciences</topic><topic>Swimming - physiology</topic><topic>Tabes Dorsalis - congenital</topic><topic>Tabes Dorsalis - pathology</topic><topic>Tabes Dorsalis - physiopathology</topic><topic>Vestibular Diseases - pathology</topic><topic>Vestibular Diseases - physiopathology</topic><topic>Vestibular Function Tests</topic><topic>Vestibular Nuclei - abnormalities</topic><topic>Vestibular Nuclei - pathology</topic><topic>Vestibular Nuclei - physiopathology</topic><topic>Vestibule, Labyrinth - abnormalities</topic><topic>Vestibule, Labyrinth - pathology</topic><topic>Vestibule, Labyrinth - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaiser, Alexander</creatorcontrib><creatorcontrib>Fedrowitz, Maren</creatorcontrib><creatorcontrib>Ebert, Ulrich</creatorcontrib><creatorcontrib>Zimmermann, Elke</creatorcontrib><creatorcontrib>Hedrich, Hans-Jürgen</creatorcontrib><creatorcontrib>Wedekind, Dirk</creatorcontrib><creatorcontrib>Löscher, Wolfgang</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The European journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaiser, Alexander</au><au>Fedrowitz, Maren</au><au>Ebert, Ulrich</au><au>Zimmermann, Elke</au><au>Hedrich, Hans-Jürgen</au><au>Wedekind, Dirk</au><au>Löscher, Wolfgang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Auditory and vestibular defects in the circling (ci2) rat mutant</atitle><jtitle>The European journal of neuroscience</jtitle><addtitle>Eur J Neurosci</addtitle><date>2001-10</date><risdate>2001</risdate><volume>14</volume><issue>7</issue><spage>1129</spage><epage>1142</epage><pages>1129-1142</pages><issn>0953-816X</issn><eissn>1460-9568</eissn><abstract>The circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behaviour, locomotor hyperactivity, ataxia and stereotypic head‐movement. These abnormal behaviours occur in phases or bursts either spontaneously or in response to stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviours. We have previously found that ci2/ci2 rats of both genders have a lower tissue content of dopamine in the striatum ipsilateral to the preferred direction of rotation, indicating that the rats turn away from the brain hemisphere with higher striatal dopaminergic activity. In view of the similarities of the motor syndrome of the ci2/ci2 mutant rat to that of mouse deafness mutants, the present study evaluated the hearing ability of the circling rat mutant by recording brainstem auditory‐evoked potentials. To test for vestibular dysfunction, a swimming test was conducted. Histological methods were used to examine the cochlear and vestibular parts of the inner ear and the cochlear and vestibular brainstem nuclei for defects. The absence of auditory‐evoked potentials demonstrated a complete hearing loss in the adult ci2/ci2 mutant rat, whereas heterozygous littermates exhibited auditory‐evoked potentials with thresholds resembling those of other laboratory strains. Furthermore, the mutant rats were unable to swim. Histological analysis of the inner ear of adult mutants revealed virtually complete loss of the cochlear neuroepithelium, while no such hair cell degeneration was seen in the vestibular parts of the inner ear. However, part of the vestibular hair cells showed protrusions into the endolymphatic space, suggesting alterations in the cytoskeletal architecture. The histological findings in mutant circling rats strongly indicate that the hearing loss of the mutants is of the sensory neural type, the most prevalent type of hearing loss. In the cochlear nuclei of the brain stem of mutant rats, neurons exhibited an abnormal shape, reduced size and increased density compared to controls. In contrast, no abnormal neuronal morphology was seen in the vestibular nuclei, but a significantly reduced neuronal density was found in the medial vestibular nucleus. Abnormal vestibular function would be a likely explanation for the disturbed balance of mutant rats as exemplified by the ataxia and the inability to swim, whereas the previous data on these rats strongly indicate an involvement of the basal ganglia in the abnormal circling behaviour. The genetic defect in the mutant rats, thus, results in a clinical syndrome with features also seen in human genetic disorders with deafness and hyperkinesia, making the ci2/ci2 rat an excellent model for investigating both cochlear/vestibular dysfunction and hyperkinetic movement disorders.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>11683905</pmid><doi>10.1046/j.0953-816x.2001.01726.x</doi><tpages>14</tpages></addata></record> |
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subjects | Animals cochlea Cochlea - abnormalities Cochlea - pathology Cochlea - physiopathology cochlear nuclei Cochlear Nucleus - abnormalities Cochlear Nucleus - pathology Cochlear Nucleus - physiopathology Deafness - pathology Deafness - physiopathology Disease Models, Animal dopamine Evoked Potentials, Auditory - genetics Female hearing loss Male Rats Rats, Mutant Strains - abnormalities Rats, Mutant Strains - metabolism rotational behaviour Space life sciences Swimming - physiology Tabes Dorsalis - congenital Tabes Dorsalis - pathology Tabes Dorsalis - physiopathology Vestibular Diseases - pathology Vestibular Diseases - physiopathology Vestibular Function Tests Vestibular Nuclei - abnormalities Vestibular Nuclei - pathology Vestibular Nuclei - physiopathology Vestibule, Labyrinth - abnormalities Vestibule, Labyrinth - pathology Vestibule, Labyrinth - physiopathology |
title | Auditory and vestibular defects in the circling (ci2) rat mutant |
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