Parkin is protective against proteotoxic stress in a transgenic zebrafish model.
Mutations in the gene encoding the E3 ubiquitin ligase parkin (PARK2) are responsible for the majority of autosomal recessive parkinsonism. Similarly to other knockout mouse models of PD-associated genes, parkin knockout mice do not show a substantial neuropathological or behavioral phenotype, while...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-07-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2912770?pdf=render |
| _version_ | 1811197012497924096 |
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| author | Mareike E Fett Anna Pilsl Dominik Paquet Frauke van Bebber Christian Haass Jörg Tatzelt Bettina Schmid Konstanze F Winklhofer |
| author_facet | Mareike E Fett Anna Pilsl Dominik Paquet Frauke van Bebber Christian Haass Jörg Tatzelt Bettina Schmid Konstanze F Winklhofer |
| author_sort | Mareike E Fett |
| collection | DOAJ |
| description | Mutations in the gene encoding the E3 ubiquitin ligase parkin (PARK2) are responsible for the majority of autosomal recessive parkinsonism. Similarly to other knockout mouse models of PD-associated genes, parkin knockout mice do not show a substantial neuropathological or behavioral phenotype, while loss of parkin in Drosophila melanogaster leads to a severe phenotype, including reduced lifespan, apoptotic flight muscle degeneration and male sterility. In order to study the function of parkin in more detail and to address possible differences in its role in different species, we chose Danio rerio as a different vertebrate model system.We first cloned zebrafish parkin to compare its biochemical and functional aspects with that of human parkin. By using an antisense knockdown strategy we generated a zebrafish model of parkin deficiency (knockdown efficiency between 50% and 60%) and found that the transient knockdown of parkin does not cause morphological or behavioral alterations. Specifically, we did not observe a loss of dopaminergic neurons in parkin-deficient zebrafish. In addition, we established transgenic zebrafish lines stably expressing parkin by using a Gal4/UAS-based bidirectional expression system. While parkin-deficient zebrafish are more vulnerable to proteotoxicity, increased parkin expression protected transgenic zebrafish from cell death induced by proteotoxic stress.Similarly to human parkin, zebrafish parkin is a stress-responsive protein which protects cells from stress-induced cell death. Our transgenic zebrafish model is a novel tool to characterize the protective capacity of parkin in vivo. |
| first_indexed | 2024-04-12T01:07:59Z |
| format | Article |
| id | doaj.art-88d7d03040ee4968a2ef81a834585572 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T01:07:59Z |
| publishDate | 2010-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-88d7d03040ee4968a2ef81a8345855722022-12-22T03:54:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-07-0157e1178310.1371/journal.pone.0011783Parkin is protective against proteotoxic stress in a transgenic zebrafish model.Mareike E FettAnna PilslDominik PaquetFrauke van BebberChristian HaassJörg TatzeltBettina SchmidKonstanze F WinklhoferMutations in the gene encoding the E3 ubiquitin ligase parkin (PARK2) are responsible for the majority of autosomal recessive parkinsonism. Similarly to other knockout mouse models of PD-associated genes, parkin knockout mice do not show a substantial neuropathological or behavioral phenotype, while loss of parkin in Drosophila melanogaster leads to a severe phenotype, including reduced lifespan, apoptotic flight muscle degeneration and male sterility. In order to study the function of parkin in more detail and to address possible differences in its role in different species, we chose Danio rerio as a different vertebrate model system.We first cloned zebrafish parkin to compare its biochemical and functional aspects with that of human parkin. By using an antisense knockdown strategy we generated a zebrafish model of parkin deficiency (knockdown efficiency between 50% and 60%) and found that the transient knockdown of parkin does not cause morphological or behavioral alterations. Specifically, we did not observe a loss of dopaminergic neurons in parkin-deficient zebrafish. In addition, we established transgenic zebrafish lines stably expressing parkin by using a Gal4/UAS-based bidirectional expression system. While parkin-deficient zebrafish are more vulnerable to proteotoxicity, increased parkin expression protected transgenic zebrafish from cell death induced by proteotoxic stress.Similarly to human parkin, zebrafish parkin is a stress-responsive protein which protects cells from stress-induced cell death. Our transgenic zebrafish model is a novel tool to characterize the protective capacity of parkin in vivo.http://europepmc.org/articles/PMC2912770?pdf=render |
| spellingShingle | Mareike E Fett Anna Pilsl Dominik Paquet Frauke van Bebber Christian Haass Jörg Tatzelt Bettina Schmid Konstanze F Winklhofer Parkin is protective against proteotoxic stress in a transgenic zebrafish model. PLoS ONE |
| title | Parkin is protective against proteotoxic stress in a transgenic zebrafish model. |
| title_full | Parkin is protective against proteotoxic stress in a transgenic zebrafish model. |
| title_fullStr | Parkin is protective against proteotoxic stress in a transgenic zebrafish model. |
| title_full_unstemmed | Parkin is protective against proteotoxic stress in a transgenic zebrafish model. |
| title_short | Parkin is protective against proteotoxic stress in a transgenic zebrafish model. |
| title_sort | parkin is protective against proteotoxic stress in a transgenic zebrafish model |
| url | http://europepmc.org/articles/PMC2912770?pdf=render |
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