ArticleScientific reports2017
Knockout of the epilepsy gene Depdc5 in mice causes severe embryonic dysmorphology with hyperactivity of mTORC1 signalling.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy.The Journal of clinical investigation · 2018Trial
- Mosaic human cortical organoids model mTOR-related focal cortical dysplasia through DEPDC5 deletion.Brain : a journal of neurology · 2026Article
- Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis.Cell death and differentiation · 2026Article
- DEPDC5: Modeling of the Two-Hit Wonder in Cortical Organoids.Epilepsy currents · 2026Article
- Early death and neuronal abnormalities inbioRxiv : the preprint server for biology · 2025Article
- The transcriptomic signature of DEPDC5 KO induced mTOR hyperactivation in human neurons and its response to rapamycin treatment.Epilepsia · 2025Article
- Emerging Role of Tripartite Synaptic Transmission in the Pathomechanism of Autosomal-Dominant Sleep-Related Hypermotor Epilepsy.International journal of molecular sciences · 2025Review
- Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma.Nature communications · 2025Article
- DEPDC5 regulates the strength of excitatory synaptic transmission by interacting with ubiquitin-specific protease 46.Neurobiology of disease · 2025Article
- Review
- Neuronal cell type specific roles for Nprl2 in neurodevelopmental disorder-relevant behaviors.Neurobiology of disease · 2025Article
- Construction of a diagnostic model for temporal lobe epilepsy using interpretable deep learning: disease-associated markers identification.Frontiers in artificial intelligence · 2025Article
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- The Role of Circular RNA for Early Diagnosis and Improved Management of Patients with Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- Functional characterization of novel NPRL3 mutations identified in three families with focal epilepsy.Science China. Life sciences · 2023Article
- Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria.Human molecular genetics · 2023Article
- Neurophysiological assessment of cortical activity in DEPDC5- and NPRL3-related epileptic mTORopathies.Orphanet journal of rare diseases · 2023Article
- Modeling genetic mosaicism of the mammalian target of rapamycin pathway in the cerebral cortex.Frontiers in mammal science · 2023Article
- SZT2 maintains hematopoietic stem cell homeostasis via nutrient-mediated mTORC1 regulation.The Journal of clinical investigation · 2022Article
- Article
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11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DEPDC5 mutations have recently been shown to cause epilepsy in humans. Evidence from in vitro studies has implicated DEPDC5 as a negative regulator of mTORC1 during amino acid insufficiency as part of the GATOR1 complex. To investigate the role of DEPDC5 in vivo we generated a null mouse model using targeted CRISPR mutagenesis. Depdc5 homozygotes display severe phenotypic defects between 12.5-15.5 dpc, including hypotrophy, anaemia, oedema, and cranial dysmorphology as well as blood and lymphatic vascular defects. mTORC1 hyperactivity was observed in the brain of knockout embryos and in fibroblasts and neurospheres isolated from knockout embryos and cultured in nutrient deprived conditions. Heterozygous mice appeared to be normal and we found no evidence of increased susceptibility to seizures or tumorigenesis. Together, these data support mTORC1 hyperactivation as the likely pathogenic mechanism that underpins DEPDC5 loss of function in humans and highlights the potential utility of mTORC1 inhibitors in the treatment of DEPDC5-associated epilepsy.
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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.