p53 Inactivation leads to impaired motor synchronization in mice
We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53‐null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This def...
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| Veröffentlicht in: | The European journal of neuroscience 2003-05, Vol.17 (10), p.2135-2146 |
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| container_title | The European journal of neuroscience |
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| creator | Campana, Aline L. M. Rondi-Reig, Laure Tobin, Christine Lohof, Ann M. Picquet, Florence Falempin, Maurice Weitzman, Jonathan B. Mariani, Jean |
| description | We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53‐null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo‐cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin‐α, into the cerebellum of wild‐type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization. |
| doi_str_mv | 10.1046/j.1460-9568.2003.02631.x |
| format | Article |
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M. ; Rondi-Reig, Laure ; Tobin, Christine ; Lohof, Ann M. ; Picquet, Florence ; Falempin, Maurice ; Weitzman, Jonathan B. ; Mariani, Jean</creator><creatorcontrib>Campana, Aline L. M. ; Rondi-Reig, Laure ; Tobin, Christine ; Lohof, Ann M. ; Picquet, Florence ; Falempin, Maurice ; Weitzman, Jonathan B. ; Mariani, Jean</creatorcontrib><description>We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53‐null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo‐cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin‐α, into the cerebellum of wild‐type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization.</description><identifier>ISSN: 0953-816X</identifier><identifier>EISSN: 1460-9568</identifier><identifier>DOI: 10.1046/j.1460-9568.2003.02631.x</identifier><identifier>PMID: 12786980</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science, Ltd</publisher><subject>Animals ; Benzothiazoles ; cerebellum ; Cerebellum - pathology ; Cerebellum - physiopathology ; Cognitive Sciences ; Lameness, Animal - pathology ; Lameness, Animal - physiopathology ; Life Sciences ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; motor behaviour ; Motor Neurons - pathology ; Motor Neurons - physiology ; Muscle Fibers, Fast-Twitch - pathology ; Muscle, Skeletal - innervation ; Muscle, Skeletal - pathology ; Neuromuscular Junction - pathology ; Neurons and Cognition ; Olivary Nucleus - pathology ; Olivary Nucleus - physiopathology ; Organ Culture Techniques ; p53 ; p53KO ; pifithrin ; Thiazoles - pharmacology ; Toluene - analogs & derivatives ; Toluene - pharmacology ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Walking</subject><ispartof>The European journal of neuroscience, 2003-05, Vol.17 (10), p.2135-2146</ispartof><rights>Federation of European Neuroscience Societies</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4701-f46683f02a85c161f0d302ea43c0e8e69ce85590f1b74a0e048b3cac3ae92cf43</citedby><cites>FETCH-LOGICAL-c4701-f46683f02a85c161f0d302ea43c0e8e69ce85590f1b74a0e048b3cac3ae92cf43</cites><orcidid>0000-0002-2701-1581 ; 0000-0003-1006-0501 ; 0000-0002-0994-7706</orcidid></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.1460-9568.2003.02631.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1460-9568.2003.02631.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12786980$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00078473$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Campana, Aline L. M.</creatorcontrib><creatorcontrib>Rondi-Reig, Laure</creatorcontrib><creatorcontrib>Tobin, Christine</creatorcontrib><creatorcontrib>Lohof, Ann M.</creatorcontrib><creatorcontrib>Picquet, Florence</creatorcontrib><creatorcontrib>Falempin, Maurice</creatorcontrib><creatorcontrib>Weitzman, Jonathan B.</creatorcontrib><creatorcontrib>Mariani, Jean</creatorcontrib><title>p53 Inactivation leads to impaired motor synchronization in mice</title><title>The European journal of neuroscience</title><addtitle>Eur J Neurosci</addtitle><description>We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53‐null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo‐cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin‐α, into the cerebellum of wild‐type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization.</description><subject>Animals</subject><subject>Benzothiazoles</subject><subject>cerebellum</subject><subject>Cerebellum - pathology</subject><subject>Cerebellum - physiopathology</subject><subject>Cognitive Sciences</subject><subject>Lameness, Animal - pathology</subject><subject>Lameness, Animal - physiopathology</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Motor Activity</subject><subject>motor behaviour</subject><subject>Motor Neurons - pathology</subject><subject>Motor Neurons - physiology</subject><subject>Muscle Fibers, Fast-Twitch - pathology</subject><subject>Muscle, Skeletal - innervation</subject><subject>Muscle, Skeletal - pathology</subject><subject>Neuromuscular Junction - pathology</subject><subject>Neurons and Cognition</subject><subject>Olivary Nucleus - pathology</subject><subject>Olivary Nucleus - physiopathology</subject><subject>Organ Culture Techniques</subject><subject>p53</subject><subject>p53KO</subject><subject>pifithrin</subject><subject>Thiazoles - pharmacology</subject><subject>Toluene - analogs & derivatives</subject><subject>Toluene - pharmacology</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Walking</subject><issn>0953-816X</issn><issn>1460-9568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS1ERZfCV0A5ITgkjGPHdg5ItKV_WS2XonIbeb2O6iWJt3a27PbTNyGr7Q315JH9ezOe9whJKGQUuPiyzCgXkJaFUFkOwDLIBaPZ5hWZ7B9ekwmUBUsVFb8PydsYlwCgBC_ekEOaSyVKBRPybVWw5KrVpnMPunO-TWqrFzHpfOKalXbBLpLGdz4kcduau-Bb9zhyrk0aZ-w7clDpOtr3u_OI_Do_uzm9TKc_L65Oj6ep4RJoWnEhFKsg16owVNAKFgxyqzkzYJUVpbGqKEqo6FxyDRa4mjOjDdO2zE3F2RH5PPa90zWugmt02KLXDi-Ppzjc9dtJxSV7oD37cWRXwd-vbeywcdHYutat9euIkjFJKZU9-Om_IFW9Y0xAqXpUjagJPsZgq_0nKOAQCi5x8B4H73EIBf-Fgpte-mE3ZT1v7OJZuEuhB76OwF9X2-2LG-PZ9Wyoen066l3s7Gav1-EPCslkgbezCzw_-X6ibmc3-IM9AdSfqC8</recordid><startdate>200305</startdate><enddate>200305</enddate><creator>Campana, Aline L. M.</creator><creator>Rondi-Reig, Laure</creator><creator>Tobin, Christine</creator><creator>Lohof, Ann M.</creator><creator>Picquet, Florence</creator><creator>Falempin, Maurice</creator><creator>Weitzman, Jonathan B.</creator><creator>Mariani, Jean</creator><general>Blackwell Science, Ltd</general><general>Wiley</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><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-2701-1581</orcidid><orcidid>https://orcid.org/0000-0003-1006-0501</orcidid><orcidid>https://orcid.org/0000-0002-0994-7706</orcidid></search><sort><creationdate>200305</creationdate><title>p53 Inactivation leads to impaired motor synchronization in mice</title><author>Campana, Aline L. M. ; Rondi-Reig, Laure ; Tobin, Christine ; Lohof, Ann M. ; Picquet, Florence ; Falempin, Maurice ; Weitzman, Jonathan B. ; Mariani, Jean</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4701-f46683f02a85c161f0d302ea43c0e8e69ce85590f1b74a0e048b3cac3ae92cf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Benzothiazoles</topic><topic>cerebellum</topic><topic>Cerebellum - pathology</topic><topic>Cerebellum - physiopathology</topic><topic>Cognitive Sciences</topic><topic>Lameness, Animal - pathology</topic><topic>Lameness, Animal - physiopathology</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Motor Activity</topic><topic>motor behaviour</topic><topic>Motor Neurons - pathology</topic><topic>Motor Neurons - physiology</topic><topic>Muscle Fibers, Fast-Twitch - pathology</topic><topic>Muscle, Skeletal - innervation</topic><topic>Muscle, Skeletal - pathology</topic><topic>Neuromuscular Junction - pathology</topic><topic>Neurons and Cognition</topic><topic>Olivary Nucleus - pathology</topic><topic>Olivary Nucleus - physiopathology</topic><topic>Organ Culture Techniques</topic><topic>p53</topic><topic>p53KO</topic><topic>pifithrin</topic><topic>Thiazoles - pharmacology</topic><topic>Toluene - analogs & derivatives</topic><topic>Toluene - pharmacology</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Walking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Campana, Aline L. M.</creatorcontrib><creatorcontrib>Rondi-Reig, Laure</creatorcontrib><creatorcontrib>Tobin, Christine</creatorcontrib><creatorcontrib>Lohof, Ann M.</creatorcontrib><creatorcontrib>Picquet, Florence</creatorcontrib><creatorcontrib>Falempin, Maurice</creatorcontrib><creatorcontrib>Weitzman, Jonathan B.</creatorcontrib><creatorcontrib>Mariani, Jean</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><collection>Hyper Article en Ligne (HAL)</collection><jtitle>The European journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Campana, Aline L. M.</au><au>Rondi-Reig, Laure</au><au>Tobin, Christine</au><au>Lohof, Ann M.</au><au>Picquet, Florence</au><au>Falempin, Maurice</au><au>Weitzman, Jonathan B.</au><au>Mariani, Jean</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53 Inactivation leads to impaired motor synchronization in mice</atitle><jtitle>The European journal of neuroscience</jtitle><addtitle>Eur J Neurosci</addtitle><date>2003-05</date><risdate>2003</risdate><volume>17</volume><issue>10</issue><spage>2135</spage><epage>2146</epage><pages>2135-2146</pages><issn>0953-816X</issn><eissn>1460-9568</eissn><abstract>We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53‐null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo‐cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin‐α, into the cerebellum of wild‐type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science, Ltd</pub><pmid>12786980</pmid><doi>10.1046/j.1460-9568.2003.02631.x</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2701-1581</orcidid><orcidid>https://orcid.org/0000-0003-1006-0501</orcidid><orcidid>https://orcid.org/0000-0002-0994-7706</orcidid></addata></record> |
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| identifier | ISSN: 0953-816X |
| ispartof | The European journal of neuroscience, 2003-05, Vol.17 (10), p.2135-2146 |
| issn | 0953-816X 1460-9568 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Benzothiazoles cerebellum Cerebellum - pathology Cerebellum - physiopathology Cognitive Sciences Lameness, Animal - pathology Lameness, Animal - physiopathology Life Sciences Male Mice Mice, Inbred C57BL Mice, Knockout Motor Activity motor behaviour Motor Neurons - pathology Motor Neurons - physiology Muscle Fibers, Fast-Twitch - pathology Muscle, Skeletal - innervation Muscle, Skeletal - pathology Neuromuscular Junction - pathology Neurons and Cognition Olivary Nucleus - pathology Olivary Nucleus - physiopathology Organ Culture Techniques p53 p53KO pifithrin Thiazoles - pharmacology Toluene - analogs & derivatives Toluene - pharmacology Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Walking |
| title | p53 Inactivation leads to impaired motor synchronization in mice |
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