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Age, brain region, and gene dosage-differential transcriptomic changes in Shank3-mutant mice
Taesun Yoo1, Ye-Eun Yoo1, Hyojin Kang2
1Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, South Korea.
Frontiers in Molecular Neuroscience
|October 31, 2022
Summary
Shank3 mutations impact brain development, causing distinct gene expression changes in young and adult mice. These transcriptomic shifts vary by age, brain region, and Shank3 gene dosage, offering insights into neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Shank3 protein is crucial for excitatory synapses and its dysfunction is linked to neurodevelopmental disorders like autism spectrum disorder (ASD).
- Limited understanding exists regarding how Shank3 mutations affect gene expression across different ages, brain areas, and genetic doses.
Purpose of the Study:
- To investigate transcriptomic alterations in Shank3-mutant mice at various developmental stages and brain regions.
- To compare gene expression patterns with those observed in ASD.
Main Methods:
- RNA sequencing was performed on forebrains of juvenile and adult homozygous Shank3-mutant mice.
- Transcriptomes of prefrontal cortex, hippocampus, and striatum were analyzed in adult heterozygous and homozygous Shank3-mutant mice.
Main Results:
- Juvenile Shank3 mutant transcriptomes showed reverse-ASD patterns with synaptic upregulation and ribosome/mitochondria downregulation.
- Adult transcriptomes exhibited ASD-like patterns with opposite molecular changes.
- Differential transcriptomic changes were observed in specific brain regions (prefrontal, hippocampal, striatal) and varied between heterozygous and homozygous mutants.
Conclusions:
- Transcriptomic changes in Shank3-mutant mice are complex and depend on age, brain region, and Shank3 gene dosage.
- These findings provide a detailed molecular basis for understanding Shank3-related neurodevelopmental disorders.
