ArticleThe Journal of clinical investigation2011
Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 179 citations in OpenAlex.
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- The Role of mTOR Signaling in Tumor-Induced Alterations to Neuronal Function in Diffusely Infiltrating Glioma.Biomedicines · 2025Review
- Single nuclei transcriptomics reveals cellular diversity in TSC subependymal giant cell astrocytomas.iScience · 2025Article
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- TSC-mTORC1 Pathway in Postnatal V-SVZ Neurodevelopment.Biomolecules · 2025Review
- Focal postnatal deletion ofFrontiers in molecular neuroscience · 2025Article
- Single unit-derived connectivity networks in tuberous sclerosis complex reveal propensity for network hypersynchrony driven by tuber-tuber interactions.Scientific reports · 2024Article
- Cytoplasmic vacuolization and ectopic formation of perineuronal nets are characteristic pathologies of cytomegalic neurons in tuberous sclerosis.Journal of neuropathology and experimental neurology · 2024Article
- Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases.Journal of translational medicine · 2024Review
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- Modeling genetic mosaicism of the mammalian target of rapamycin pathway in the cerebral cortex.Frontiers in mammal science · 2023Article
- Neurodevelopmental disorders: 2023 update.Free neuropathology · 2023Article
- Human cerebral organoids - a new tool for clinical neurology research.Nature reviews. Neurology · 2022Review
- Synaptic hyperexcitability of cytomegalic pyramidal neurons contributes to epileptogenesis in tuberous sclerosis complex.Cell reports · 2022Article
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- Rare CACNA1H and RELN variants interact through mTORC1 pathway in oligogenic autism spectrum disorder.Translational psychiatry · 2022Article
- Amplification of human interneuron progenitors promotes brain tumors and neurological defects.Science (New York, N.Y.) · 2022Article
- Identifying the temporal electrophysiological and molecular changes that contribute to TSC-associated epileptogenesis.JCI insight · 2021Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by mutations in Tsc1 or Tsc2 that lead to mammalian target of rapamycin (mTOR) hyperactivity. Patients with TSC suffer from intractable seizures resulting from cortical malformations known as tubers, but research into how these tubers form has been limited because of the lack of an animal model. To address this limitation, we used in utero electroporation to knock out Tsc1 in selected neuronal populations in mice heterozygous for a mutant Tsc1 allele that eliminates the Tsc1 gene product at a precise developmental time point. Knockout of Tsc1 in single cells led to increased mTOR activity and soma size in the affected neurons. The mice exhibited white matter heterotopic nodules and discrete cortical tuber-like lesions containing cytomegalic and multinucleated neurons with abnormal dendritic trees resembling giant cells. Cortical tubers in the mutant mice did not exhibit signs of gliosis. Furthermore, phospho-S6 immunoreactivity was not upregulated in Tsc1-null astrocytes despite a lower seizure threshold. Collectively, these data suggest that a double-hit strategy to eliminate Tsc1 in discrete neuronal populations generates TSC-associated cortical lesions, providing a model to uncover the mechanisms of lesion formation and cortical hyperexcitability. In addition, the absence of glial reactivity argues against a contribution of astrocytes to lesion-associated hyperexcitability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.