PUBLICATION

CPT2 Deficiency Modeled in Zebrafish: Abnormal Neural Development, Electrical Activity, Behavior, and Schizophrenia-Related Gene Expression

Authors
Baker, C.E., Marta, A.G., Zimmerman, N.D., Korade, Z., Mathy, N.W., Wilton, D., Simeone, T., Kochvar, A., Kramer, K.L., Stessman, H.A.F., Shibata, A.
ID
ZDB-PUB-240901-6
Date
2024
Source
Biomolecules   14(8): (Journal)
Registered Authors
Kramer, Kenneth
Keywords
CPT2 deficiency, brain development, carnitine palmitoyltransferase, neurodegenerative disease, schizophrenia-related gene expression, seizure-like activity, zebrafish, β-oxidation
MeSH Terms
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Schizophrenia*/genetics
  • Schizophrenia*/metabolism
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Brain*/growth & development
  • Brain*/metabolism
  • Animals
  • Carnitine O-Palmitoyltransferase*/deficiency
  • Carnitine O-Palmitoyltransferase*/genetics
  • Carnitine O-Palmitoyltransferase*/metabolism
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental
  • Behavior, Animal
  • Gene Knockdown Techniques
(all 17)
PubMed
39199302 Full text @ Biomolecules
Abstract
Carnitine palmitoyltransferase 2 (CPT2) is an inner mitochondrial membrane protein of the carnitine shuttle and is involved in the beta-oxidation of long chain fatty acids. Beta-oxidation provides an alternative pathway of energy production during early development and starvation. CPT2 deficiency is a genetic disorder that we recently showed can be associated with schizophrenia. We hypothesize that CPT2 deficiency during early brain development causes transcriptional, structural, and functional abnormalities that may contribute to a CNS environment that is susceptible to the emergence of schizophrenia. To investigate the effect of CPT2 deficiency on early vertebrate development and brain function, CPT2 was knocked down in a zebrafish model system. CPT2 knockdown resulted in abnormal lipid utilization and deposition, reduction in body size, and abnormal brain development. Axonal projections, neurotransmitter synthesis, electrical hyperactivity, and swimming behavior were disrupted in CPT2 knockdown zebrafish. RT-qPCR analyses showed significant increases in the expression of schizophrenia-associated genes in CPT2 knockdown compared to control zebrafish. Taken together, these data demonstrate that zebrafish are a useful model for studying the importance of beta-oxidation for early vertebrate development and brain function. This study also presents novel findings linking CPT2 deficiency to the regulation of schizophrenia and neurodegenerative disease-associated genes.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
cpt2MO1-cpt2MRPHLNO
cpt2MO2-cpt2MRPHLNO
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Fish
No data available
Antibodies
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available
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Citation
Baker, C.E., Marta, A.G., Zimmerman, N.D., Korade, Z., Mathy, N.W., Wilton, D., Simeone, T., Kochvar, A., Kramer, K.L., Stessman, H.A.F., Shibata, A. (2024) CPT2 Deficiency Modeled in Zebrafish: Abnormal Neural Development, Electrical Activity, Behavior, and Schizophrenia-Related Gene Expression. Biomolecules. 14(8):.