Cloning and expression analysis of a Parkinson’s disease gene, uch-L1, and its promoter in zebrafish

Son, Ok-Lye; Kim, Hyun-Taek; Ji, Mi-Hyun; Yoo, Kyeong-Won; Rhee, Myungchull; Kim, Cheol-Hee

doi:10.1016/j.bbrc.2003.10.163

Cited by 58 publications

(27 citation statements)

References 24 publications

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“…The conditional LRRK2 G2019S model [27] was reported to have no obvious neuropathological or motor abnormalities at 12 months of age. Over-expression of UCH-L1 in zebrafish did not result in a discernible phenotypic effect [44]. Therefore, the previous vertebrate models did not show, in a consistent fashion, the progressive loss of nigrostriatal dopaminergic neurons and motor defects.…”

Section: Discussionmentioning

confidence: 83%

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect

et al. 2010

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LRRK2 plays an important role in Parkinson's disease (PD), but its biological functions are largely unknown. Here, we cloned the homolog of human LRRK2, characterized its expression, and investigated its biological functions in zebrafish. The blockage of zebrafish LRRK2 (zLRRK2) protein by morpholinos caused embryonic lethality and severe developmental defects such as growth retardation and loss of neurons. In contrast, the deletion of the WD40 domain of zLRRK2 by morpholinos targeting splicing did not induce severe embryonic developmental defects; rather it caused Parkinsonism-like phenotypes, including loss of dopaminergic neurons in diencephalon and locomotion defects. These neurodegenerative and locomotion defects could be rescued by over-expressing zLRRK2 or hLRRK2 mRNA. The administration of L-dopa could also rescue the locomotion defects, but not the neurodegeneration. Taken together, our results demonstrate that zLRRK2 is an ortholog of hLRRK2 and that the deletion of WD40 domain of zLRRK2 provides a disease model for PD.

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Section: Discussionmentioning

confidence: 83%

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect

et al. 2010

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“…In zebrafish, UCH-L1 mRNA was expressed in neuronal cells at 1 d.p.f. (Son et al 2003). UCH-L1 was detected in the diencephalon and ventral region of the mid and hindbrain, which are associated with motoneuron development (although which mammalian motoneurons these were correlated with was not investigated).…”

Section: Zebrafish Neurodegenerative Disease Modelsmentioning

confidence: 99%

Zebrafish: An in vivo model for the study of neurological diseases

Best¹

2008

NDT

179

112

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Abstract:As the population ages, there is a growing need for effective therapies for the treatment of neurological diseases. A limited number of therapeutics are currently available to improve cognitive function and research is limited by the need for in vivo models. Zebrafi sh have recently become a focus of neurobehavioral studies since larvae display neuropathological and behavioral phenotypes that are quantifi able and relate to those seen in man. Due to the small size of Zebrafi sh larvae, assays can be undertaken in 96 well plates and as the larvae can live in as little as 200 µl of fl uid, only a few milligrams of compound are needed for screening. Thus in vivo analysis of the effects of compounds can be undertaken at much earlier stages in the drug discovery process. This review will look at the utility of the zebrafi sh in the study of neurological diseases and its role in improving the throughput of candidate compounds in in vivo screens.

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“…We and others have detected closely related homologues of the human PD genes in zebrafish. Highly conserved homologous gene sequences have been identified for the PD genes ubiquitin C‐terminal hydrolase L1 ( UCH‐L1 ) (Son et al. 2003) and DJ‐1 (Bai et al.…”

Section: Zebrafish As a New Animal Model For Parkinson’s Diseasementioning

confidence: 99%

Zebrafish as a new animal model for movement disorders

Flinn

Bretaud

et al. 2008

Journal of Neurochemistry

125

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The zebrafish, long recognized as a model organism for the analysis of basic developmental processes, is now also emerging as an alternative animal model for human diseases. This review will first provide an overview of the particular characteristics of zebrafish in general and their dopaminergic nervous system in particular. We will then summarize all work undertaken so far to establish zebrafish as a new animal model for movement disorders and will finally emphasize its particular strength -amenability to high throughput in vivo drug screening.

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Cloning and expression analysis of a Parkinson’s disease gene, uch-L1, and its promoter in zebrafish

Cited by 58 publications

References 24 publications

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect

Zebrafish: An in vivo model for the study of neurological diseases

Zebrafish as a new animal model for movement disorders

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