PUBLICATION
Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536
- Authors
- Kim, T.Y., Roychaudhury, A., Kim, H.T., Choi, T.I., Baek, S.T., Thyme, S.B., Kim, C.H.
- ID
- ZDB-PUB-240209-9
- Date
- 2024
- Source
- Translational psychiatry 14: 8282 (Journal)
- Registered Authors
- Kim, Cheol-Hee, Kim, Hyun-Taek, Thyme, Summer
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified/metabolism
- Brain/metabolism
- Cerebellum*/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38331943 Full text @ Transl Psychiatry
Citation
Kim, T.Y., Roychaudhury, A., Kim, H.T., Choi, T.I., Baek, S.T., Thyme, S.B., Kim, C.H. (2024) Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536. Translational psychiatry. 14:8282.
Abstract
Genetic variants in ZNF536 contribute to the risk for neuropsychiatric disorders such as schizophrenia, autism, and others. The role of this putative transcriptional repressor in brain development and function is, however, largely unknown. We generated znf536 knockout (KO) zebrafish and studied their behavior, brain anatomy, and brain function. Larval KO zebrafish showed a reduced ability to compete for food, resulting in decreased total body length and size. This phenotype can be rescued by segregating the homozygous KO larvae from their wild-type and heterozygous siblings, enabling studies of adult homozygous KO animals. In adult KO zebrafish, we observed significant reductions in anxiety-like behavior and social interaction. These znf536 KO zebrafish have decreased cerebellar volume, corresponding to decreased populations of specific neuronal cells, especially in the valvular cerebelli (Va). Finally, using a Tg[mbp:mgfp] line, we identified a previously undetected myelin structure located bilaterally within the Va, which also displayed a reduction in volume and disorganization in KO zebrafish. These findings indicate an important role for ZNF536 in brain development and implicate the cerebellum in the pathophysiology of neuropsychiatric disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping