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Gene Expression Profiling in the Cortex of Fabp4 Knockout Mice
Hinako Kirikae1, Xiaofeng He1, Tetsuo Ohnishi2
1Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
Neuropsychopharmacology Reports
|February 8, 2025
Summary
Fatty acid binding protein 4 (Fabp4) is not found in the brain, but its absence alters brain gene expression. This suggests systemic lipid metabolism influences neurodevelopment and disorders like autism spectrum disorder (ASD).
Area of Science:
- Neuroscience
- Metabolic Regulation
- Epigenetics
Background:
- Fatty acid binding protein 4 (Fabp4) is crucial for peripheral lipid metabolism.
- Its role in brain function is largely unknown.
- Fabp4 knockout (KO) mice exhibit autism-like behaviors.
Purpose of the Study:
- Investigate Fabp4 expression in the adult mouse brain.
- Analyze gene expression changes in Fabp4 KO mice to understand its impact on brain function.
Main Methods:
- In situ hybridization to detect Fabp4 expression in mouse brain regions.
- RNA-sequencing (RNA-seq) for differential gene expression analysis in the prefrontal cortex of Fabp4 KO mice.
Main Results:
- Fabp4 expression was undetectable in the adult mouse brain.
- Fabp4 deficiency led to significant gene expression changes: 31 genes upregulated and 30 downregulated.
- Downregulated genes involved histone methylation and metabolism; upregulated genes related to synaptic organization.
Conclusions:
- Fabp4 is not directly expressed in the brain, but its deficiency impacts brain gene expression.
- Peripheral metabolic pathways and epigenetic regulation likely mediate these effects.
- Findings suggest systemic lipid metabolism influences neurodevelopmental disorders like ASD and highlight epigenetic mechanisms.
Keywords:
Fabp4 knockout (KO) miceRNA‐seqautism spectrum disorderepigenetic gene expressionsynaptic gene expression
