Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain

Suzzi, Stefano; Ahrendt, Reiner; Hans, Stefan; Semenova, Svetlana; Chekuru, Avinash; Wirsching, Paul; Kroehne, Volker; Bilican, Saygın; Sayed, Shady; Winkler, Sylke; Spieß, Sandra; Machate, Anja; Kaslin, Jan; Panula, Pertti; Brand, Michael

doi:10.1371/journal.pgen.1009794

Cited by 5 publications

(3 citation statements)

References 82 publications

(133 reference statements)

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“…There is a difficulty in understanding such autosomal dominant disease because it might not be clear whether a loss of the normal function of the gene is a major cause of the phenotype or whether a gain of toxic function can explain the disease. There have been several zebrafish models of Lrrk2, but we will await further evaluations and consistent findings [114][115][116][117].…”

Section: Zebrafish and Medaka Models Of Parkinson's Diseasementioning

confidence: 83%

Zebrafish, Medaka and Turquoise Killifish for Understanding Human Neurodegenerative/Neurodevelopmental Disorders

Kodera

Matsui

2022

IJMS

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In recent years, small fishes such as zebrafish and medaka have been widely recognized as model animals. They have high homology in genetics and tissue structure with humans and unique features that mammalian model animals do not have, such as transparency of embryos and larvae, a small body size and ease of experiments, including genetic manipulation. Zebrafish and medaka have been used extensively in the field of neurology, especially to unveil the mechanisms of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, and recently, these fishes have also been utilized to understand neurodevelopmental disorders such as autism spectrum disorder. The turquoise killifish has emerged as a new and unique model animal, especially for ageing research due to its unique life cycle, and this fish also seems to be useful for age-related neurological diseases. These small fishes are excellent animal models for the analysis of human neurological disorders and are expected to play increasing roles in this field. Here, we introduce various applications of these model fishes to improve our understanding of human neurological disorders.

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Section: Zebrafish and Medaka Models Of Parkinson's Diseasementioning

confidence: 83%

Zebrafish, Medaka and Turquoise Killifish for Understanding Human Neurodegenerative/Neurodevelopmental Disorders

Kodera

Matsui

2022

IJMS

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“…Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein interacting with parkin [ 227 , 228 ]. The studies of knockdown or knockout of lrrk2 have reported various but conflicting phenotypes in terms of the number of dopaminergic neurons [ 204 , 205 , 206 , 207 , 208 , 209 ]. Notably, the mechanism underlying the pathogenic effect of PD by LRRK2 mutation remains unknown because point mutations have been found among different domains [ 228 ].…”

Section: Small Fish Models To Study Mitochondrial Function/dysfunctionmentioning

confidence: 99%

Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders

Otsuka

Matsui

2023

IJMS

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Neurodegenerative disorders are characterized by the progressive loss of neuronal structure or function, resulting in memory loss and movement disorders. Although the detailed pathogenic mechanism has not been elucidated, it is thought to be related to the loss of mitochondrial function in the process of aging. Animal models that mimic the pathology of a disease are essential for understanding human diseases. In recent years, small fish have become ideal vertebrate models for human disease due to their high genetic and histological homology to humans, ease of in vivo imaging, and ease of genetic manipulation. In this review, we first outline the impact of mitochondrial dysfunction on the progression of neurodegenerative diseases. Then, we highlight the advantages of small fish as model organisms, and present examples of previous studies regarding mitochondria-related neuronal disorders. Lastly, we discuss the applicability of the turquoise killifish, a unique model for aging research, as a model for neurodegenerative diseases. Small fish models are expected to advance our understanding of the mitochondrial function in vivo, the pathogenesis of neurodegenerative diseases, and be important tools for developing therapies to treat diseases.

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“…Some studies reported loss of DA neurons and locomotion defects following LRRK2 knockdown, while others showed no such effects even when the same morpholino RNAs were used (Prabhudesai et al, 2016; Ren et al, 2011; Sheng et al, 2010). Subsequently, several Lrrk2‐deficient lines were established by gene editing, yet no locomotion defect or DA neuron loss was detected (Suzzi et al, 2021; Wint & Sirotkin, 2020). In contrast, the transient overexpression of wild‐type or G2019S human LRRK2 in zebrafish resulted in impaired ubiquitin–proteasome activity (Lichtenberg et al, 2011).…”

Section: Genetic Pd Models In Zebrafishmentioning

confidence: 99%

Modeling familial and sporadic Parkinson's disease in small fishes

Yamanaka,

Matsui

2023

Dev Growth Differ

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The establishment of animal models for Parkinson's disease (PD) has been challenging. Nevertheless, once established, they will serve as valuable tools for elucidating the causes and pathogenesis of PD, as well as for developing new strategies for its treatment. Following the recent discovery of a series of PD causative genes in familial cases, teleost fishes, including zebrafish and medaka, have often been used to establish genetic PD models because of their ease of breeding and gene manipulation, as well as the high conservation of gene orthologs. Some of the fish lines can recapitulate PD phenotypes, which are often more pronounced than those in rodent genetic models. In addition, a new experimental teleost fish, turquoise killifish, can be used as a sporadic PD model, because it spontaneously manifests age‐dependent PD phenotypes. Several PD fish models have already made significant contributions to the discovery of novel PD pathological features, such as cytosolic leakage of mitochondrial DNA and pathogenic phosphorylation in α‐synuclein. Therefore, utilizing various PD fish models with distinct degenerative phenotypes will be an effective strategy for identifying emerging facets of PD pathogenesis and therapeutic modalities.

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Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain

Cited by 5 publications

References 82 publications

Zebrafish, Medaka and Turquoise Killifish for Understanding Human Neurodegenerative/Neurodevelopmental Disorders

Zebrafish, Medaka and Turquoise Killifish for Understanding Human Neurodegenerative/Neurodevelopmental Disorders

Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders

Modeling familial and sporadic Parkinson's disease in small fishes

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