Dopaminergic Neuron-Specific Autophagy-Deficient Mice
None of the current genetic Parkinson’s disease (PD) models in mouse recapitulates all features of PD. Additionally, only a few of these models develop mild dopamine (DA) neurodegeneration. And the most parsimonious explanation for the lack of DA neurodegeneration in genetic PD models is a compensat...
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Veröffentlicht in: | Methods in molecular biology (Clifton, N.J.) N.J.), 2018, Vol.1759, p.173-175 |
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container_title | Methods in molecular biology (Clifton, N.J.) |
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creator | Sato, Shigeto Hattori, Nobutaka |
description | None of the current genetic Parkinson’s disease (PD) models in mouse recapitulates all features of PD. Additionally, only a few of these models develop mild dopamine (DA) neurodegeneration. And the most parsimonious explanation for the lack of DA neurodegeneration in genetic PD models is a compensatory mechanism that results from adaptive changes during development, making it hard to observe the degenerative phenotype over the life span of mice. Here, we characterize DA neuron-specific autophagy-deficient mice and provide in vivo evidence for Lewy body formation. Atg7-deficient mice demonstrate typical Lewy pathology, including endogenous synuclein and neuronal loss, which resembles PD. Furthermore DA levels are affected by dopaminergic neuronal loss. The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD. |
doi_str_mv | 10.1007/7651_2018_156 |
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The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD.</description><identifier>ISSN: 1064-3745</identifier><identifier>ISBN: 1493977490</identifier><identifier>ISBN: 9781493977499</identifier><identifier>EISSN: 1940-6029</identifier><identifier>EISBN: 9781493977505</identifier><identifier>EISBN: 1493977504</identifier><identifier>DOI: 10.1007/7651_2018_156</identifier><identifier>PMID: 29804260</identifier><language>eng</language><publisher>New York, NY: Springer New York</publisher><subject>Animals ; Atg7 ; Autophagy ; Autophagy-Related Protein 7 - genetics ; Autophagy-Related Protein 7 - metabolism ; Behavior, Animal ; Biomarkers ; Disease Models, Animal ; Dopaminergic neuron ; Dopaminergic Neurons - metabolism ; Lewy body ; Mice ; Mitochondria - genetics ; Mitochondria - metabolism ; Mouse model ; Parkinson Disease - genetics ; Parkinson Disease - metabolism ; Parkinson’s disease ; Phenotype</subject><ispartof>Methods in molecular biology (Clifton, N.J.), 2018, Vol.1759, p.173-175</ispartof><rights>Springer Science+Business Media New York 2018</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/7651_2018_156$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/7651_2018_156$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>779,780,784,793,27924,38254,41441,42510</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29804260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Saiki, Shinji</contributor><contributor>Hattori, Nobutaka</contributor><creatorcontrib>Sato, Shigeto</creatorcontrib><creatorcontrib>Hattori, Nobutaka</creatorcontrib><title>Dopaminergic Neuron-Specific Autophagy-Deficient Mice</title><title>Methods in molecular biology (Clifton, N.J.)</title><addtitle>Methods Mol Biol</addtitle><description>None of the current genetic Parkinson’s disease (PD) models in mouse recapitulates all features of PD. 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The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD.</description><subject>Animals</subject><subject>Atg7</subject><subject>Autophagy</subject><subject>Autophagy-Related Protein 7 - genetics</subject><subject>Autophagy-Related Protein 7 - metabolism</subject><subject>Behavior, Animal</subject><subject>Biomarkers</subject><subject>Disease Models, Animal</subject><subject>Dopaminergic neuron</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Lewy body</subject><subject>Mice</subject><subject>Mitochondria - genetics</subject><subject>Mitochondria - metabolism</subject><subject>Mouse model</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson’s disease</subject><subject>Phenotype</subject><issn>1064-3745</issn><issn>1940-6029</issn><isbn>1493977490</isbn><isbn>9781493977499</isbn><isbn>9781493977505</isbn><isbn>1493977504</isbn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkDlPw0AQhZdLBEJKWpQSCRlm9vSUUcIlBSiAerXerIMhPvDGRf49RgkF1ejp-_SkeYydI1wjgLkxWqHlgKlFpffYiEyKkgQZo0DtsxMkCYkGTgfsdAckwWEPQMtEGKkGbBTjJwBwRCUlHrMBpxQk13DC1KxuXFlUoV0Wfvwcurauktcm-CLv86Rb182HW26SWehzEar1-Knw4Ywd5W4Vw2h3h-z97vZt-pDMX-4fp5N50qDmOsmFx1SmPqVcSZMRLYTKMg_OeQ8SfSAtSDnKHFHOTQgLr5XTIneIaQAQQ3a57W3a-rsLcW3LIvqwWrkq1F3sd5EaUHBOvXqxU7usDAvbtEXp2o39e7UXrrZC7FG1DK3N6vorWgT7O7T9N7T4AcM0ZxE</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Sato, Shigeto</creator><creator>Hattori, Nobutaka</creator><general>Springer New York</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>2018</creationdate><title>Dopaminergic Neuron-Specific Autophagy-Deficient Mice</title><author>Sato, Shigeto ; Hattori, Nobutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1626-f3c1848c89f547b99d35bbc0aacc041ce96395a9ba99f27eedc65a63fa118e003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Atg7</topic><topic>Autophagy</topic><topic>Autophagy-Related Protein 7 - genetics</topic><topic>Autophagy-Related Protein 7 - metabolism</topic><topic>Behavior, Animal</topic><topic>Biomarkers</topic><topic>Disease Models, Animal</topic><topic>Dopaminergic neuron</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>Lewy body</topic><topic>Mice</topic><topic>Mitochondria - genetics</topic><topic>Mitochondria - metabolism</topic><topic>Mouse model</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson’s disease</topic><topic>Phenotype</topic><toplevel>online_resources</toplevel><creatorcontrib>Sato, Shigeto</creatorcontrib><creatorcontrib>Hattori, Nobutaka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Methods in molecular biology (Clifton, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sato, Shigeto</au><au>Hattori, Nobutaka</au><au>Saiki, Shinji</au><au>Hattori, Nobutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dopaminergic Neuron-Specific Autophagy-Deficient Mice</atitle><jtitle>Methods in molecular biology (Clifton, N.J.)</jtitle><addtitle>Methods Mol Biol</addtitle><date>2018</date><risdate>2018</risdate><volume>1759</volume><spage>173</spage><epage>175</epage><pages>173-175</pages><issn>1064-3745</issn><eissn>1940-6029</eissn><isbn>1493977490</isbn><isbn>9781493977499</isbn><eisbn>9781493977505</eisbn><eisbn>1493977504</eisbn><abstract>None of the current genetic Parkinson’s disease (PD) models in mouse recapitulates all features of PD. Additionally, only a few of these models develop mild dopamine (DA) neurodegeneration. And the most parsimonious explanation for the lack of DA neurodegeneration in genetic PD models is a compensatory mechanism that results from adaptive changes during development, making it hard to observe the degenerative phenotype over the life span of mice. Here, we characterize DA neuron-specific autophagy-deficient mice and provide in vivo evidence for Lewy body formation. Atg7-deficient mice demonstrate typical Lewy pathology, including endogenous synuclein and neuronal loss, which resembles PD. Furthermore DA levels are affected by dopaminergic neuronal loss. The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD.</abstract><cop>New York, NY</cop><pub>Springer New York</pub><pmid>29804260</pmid><doi>10.1007/7651_2018_156</doi><tpages>3</tpages></addata></record> |
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subjects | Animals Atg7 Autophagy Autophagy-Related Protein 7 - genetics Autophagy-Related Protein 7 - metabolism Behavior, Animal Biomarkers Disease Models, Animal Dopaminergic neuron Dopaminergic Neurons - metabolism Lewy body Mice Mitochondria - genetics Mitochondria - metabolism Mouse model Parkinson Disease - genetics Parkinson Disease - metabolism Parkinson’s disease Phenotype |
title | Dopaminergic Neuron-Specific Autophagy-Deficient Mice |
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