ArticleHuman molecular genetics2009
Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
127 citing papers in PubMed, 220 citations in OpenAlex.
- Article
- Cell Type-Specific mTORC1 Signaling and Translational Control in Synaptic Plasticity and Memory.Journal of neurochemistry · 2025Review
- High-throughput bioprinting to produce micropatterned neuroepithelial tissues and model TSC2-deficient brain malformations.Cell reports methods · 2025Article
- AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth.Developmental cell · 2025Article
- AAV hamartin gene therapy in a stochastic, cerebral mouse model of tuberous sclerosis type 1.Molecular therapy. Methods & clinical development · 2025Article
- Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome.Human molecular genetics · 2025Article
- Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate.Stem cell research & therapy · 2025Review
- The multifaceted role of mitochondria in autism spectrum disorder.Molecular psychiatry · 2025Review
- Focal postnatal deletion ofFrontiers in molecular neuroscience · 2025Article
- Transcriptomic dysregulation and autistic-like behaviors in Kmt2c haploinsufficient mice rescued by an LSD1 inhibitor.Molecular psychiatry · 2024Article
- Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome.bioRxiv : the preprint server for biology · 2024Article
- Using cortical organoids to understand the pathogenesis of malformations of cortical development.Frontiers in neuroscience · 2024Review
- Rodent Models for ASD Biomarker Development.Advances in neurobiology · 2024Review
- Article
- Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model.The Journal of clinical investigation · 2023Article
- Specific Features of Focal Cortical Dysplasia in Tuberous Sclerosis Complex.Current issues in molecular biology · 2023Review
- Modeling genetic mosaicism of the mammalian target of rapamycin pathway in the cerebral cortex.Frontiers in mammal science · 2023Article
- NPRL3 loss alters neuronal morphology, mTOR localization, cortical lamination and seizure threshold.Brain : a journal of neurology · 2022Article
- Synaptic hyperexcitability of cytomegalic pyramidal neurons contributes to epileptogenesis in tuberous sclerosis complex.Cell reports · 2022Article
- Abnormal activation of Yap/Taz contributes to the pathogenesis of tuberous sclerosis complex.Human molecular genetics · 2022Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant, tumor predisposition disorder characterized by significant neurodevelopmental brain lesions, such as tubers and subependymal nodules. The neuropathology of TSC is often associated with seizures and intellectual disability. To learn about the developmental perturbations that lead to these brain lesions, we created a mouse model that selectively deletes the Tsc2 gene from radial glial progenitor cells in the developing cerebral cortex and hippocampus. These Tsc2 mutant mice were severely runted, developed post-natal megalencephaly and died between 3 and 4 weeks of age. Analysis of brain pathology demonstrated cortical and hippocampal lamination defects, hippocampal heterotopias, enlarged dysplastic neurons and glia, abnormal myelination and an astrocytosis. These histologic abnormalities were accompanied by activation of the mTORC1 pathway as assessed by increased phosphorylated S6 in brain lysates and tissue sections. Developmental analysis demonstrated that loss of Tsc2 increased the subventricular Tbr2-positive basal cell progenitor pool at the expense of early born Tbr1-positive post-mitotic neurons. These results establish the novel concept that loss of function of Tsc2 in radial glial progenitors is one initiating event in the development of TSC brain lesions as well as underscore the importance of Tsc2 in the regulation of neural progenitor pools. Given the similarities between the mouse and the human TSC lesions, this model will be useful in further understanding TSC brain pathophysiology, testing potential therapies and identifying other genetic pathways that are altered in TSC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.