PUBLICATION
Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain
- Authors
- Suzzi, S., Ahrendt, R., Hans, S., Semenova, S.A., Chekuru, A., Wirsching, P., Kroehne, V., Bilican, S., Sayed, S., Winkler, S., Spieß, S., Machate, A., Kaslin, J., Panula, P., Brand, M.
- ID
- ZDB-PUB-210914-13
- Date
- 2021
- Source
- PLoS Genetics 17: e1009794 (Journal)
- Registered Authors
- Ahrendt, Reiner, Brand, Michael, Chekuru, Avinash, Hans, Stefan, Kaslin, Jan, Kroehne, Volker, Machate, Anja, Panula, Pertti, Semenova, Svetlana, Winkler, Sylke
- Keywords
- none
- MeSH Terms
-
- Smell/genetics
- Brain/embryology
- Brain/enzymology
- Brain/metabolism*
- Biogenic Monoamines/metabolism*
- Swimming
- Animals
- Zebrafish Proteins/genetics*
- Monoamine Oxidase/metabolism
- CRISPR-Cas Systems
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics*
- Gene Deletion*
- Larva/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- Anxiety/genetics
- PubMed
- 34516550 Full text @ PLoS Genet.
Citation
Suzzi, S., Ahrendt, R., Hans, S., Semenova, S.A., Chekuru, A., Wirsching, P., Kroehne, V., Bilican, S., Sayed, S., Winkler, S., Spieß, S., Machate, A., Kaslin, J., Panula, P., Brand, M. (2021) Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain. PLoS Genetics. 17:e1009794.
Abstract
LRRK2 gain-of-function is considered a major cause of Parkinson's disease (PD) in humans. However, pathogenicity of LRRK2 loss-of-function in animal models is controversial. Here we show that deletion of the entire zebrafish lrrk2 locus elicits a pleomorphic transient brain phenotype in maternal-zygotic mutant embryos (mzLrrk2). In contrast to lrrk2, the paralog gene lrrk1 is virtually not expressed in the brain of both wild-type and mzLrrk2 fish at different developmental stages. Notably, we found reduced catecholaminergic neurons, the main target of PD, in specific cell populations in the brains of mzLrrk2 larvae, but not adult fish. Strikingly, age-dependent accumulation of monoamine oxidase (MAO)-dependent catabolic signatures within mzLrrk2 brains revealed a previously undescribed interaction between LRRK2 and MAO biological activities. Our results highlight mzLrrk2 zebrafish as a tractable tool to study LRRK2 loss-of-function in vivo, and suggest a link between LRRK2 and MAO, potentially of relevance in the prodromic stages of PD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping