A5054956018- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Epilepsy research and treatment
- Ion channel regulation and function
- Cellular transport and secretion
- Redox biology and oxidative stress
- Pluripotent Stem Cells Research
- Amino Acid Enzymes and Metabolism
- Mitochondrial Function and Pathology
- Autoimmune Neurological Disorders and Treatments
- Zebrafish Biomedical Research Applications
- Hematopoietic Stem Cell Transplantation
- Genetic Neurodegenerative Diseases
- Virus-based gene therapy research
- Humic Substances and Bio-Organic Studies
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Immunodeficiency and Autoimmune Disorders
- MicroRNA in disease regulation
- Fungal and yeast genetics research
- RNA regulation and disease
- Genetics, Aging, and Longevity in Model Organisms
The University of Tokyo
2021-2025
Tokyo Medical and Dental University
2018-2021
Institut du Cerveau
2014-2018
Centre National de la Recherche Scientifique
2014-2018
Sorbonne Université
2014-2018
Inserm
2013-2018
Université Paris Cité
2016
University of Geneva
2014
Kyoto University
2011-2014
Institute of Laboratory Animal Science
2012
The DEPDC5 (DEP domain-containing protein 5) gene, encoding a repressor of the mTORC1 signaling pathway, has recently emerged as major gene mutated in familial focal epilepsies. We aimed to further extend role cortical dysplasias (FCDs).Seven patients from 4 families with mutations and epilepsy associated FCD were recruited investigated at clinical, neuroimaging, histopathological levels. was sequenced genomic blood brain DNA.All had drug-resistant epilepsy, 5 them underwent surgery, 1...
To study the prevalence of DEPDC5 mutations in a series 30 small European families with phenotype compatible autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).Thirty unrelated referred ADNFLE were recruited France, Italy, Germany, Belgium, and Norway. Whole-exome sequencing was performed 10 probands direct coding sequence 20 probands. Testing for nonsense-mediated messenger RNA decay (NMD) lymphoblastic cells.Exome revealed splice acceptor mutation (c.2355-2A>G) proband German...
DEP-domain containing 5 (DEPDC5), encoding a repressor of the mechanistic target rapamycin complex 1 (mTORC1) signaling pathway, has recently emerged as major gene mutated in familial focal epilepsies and cortical dysplasia. Here we established global knockout rat using TALEN technology to investigate vivo impact Depdc5-deficiency. Homozygous Depdc5(-/-) embryos died from embryonic day 14.5 due growth delay. Constitutive mTORC1 hyperactivation was evidenced brains cultured fibroblasts...
Severe combined immunodeficiency (SCID) mice, the most widely used animal model of DNA-PKcs (Prkdc) deficiency, have contributed enormously to our understanding immunodeficiency, lymphocyte development, and DNA-repair mechanisms, they are ideal hosts for allogeneic xenogeneic tissue transplantation.Here, we use zinc-finger nucleases generate rats that lack either Prkdc gene or Il2rg genes (referred as F344-scid gamma [FSG] rats).SCID show several phenotypic differences from SCID including...
Rats (Rattus norvegicus) have been widely utilized as model animals due to their physiological characteristics, making them suitable for surgical and long-term studies. They played a crucial role in biomedical research, complementing studies conducted mice. The advent of genome editing technologies has facilitated the generation genetically modified rat strains, advancing experimental animals. Among these innovations, Cre-driver models emerged powerful tools spatiotemporal control gene...
Leucin-rich, glioma inactivated 1 (LGI1) is a secreted protein linked to human seizures of both genetic and autoimmune aetiology. Mutations in the LGI1 gene are responsible for autosomal dominant temporal lobe epilepsy with auditory features, whereas autoantibodies involved limbic encephalitis, an acquired epileptic disorder associated cognitive impairment. We others previously reported that Lgi1-deficient mice have early-onset spontaneous leading premature death at 2–3 weeks age. Yet, where...
Abstract Objective DEPDC 5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in wide range inherited forms epilepsy, associated malformation cortical development certain cases. Identification frameshift, truncation, and deletion implicates haploinsufficiency the etiology epilepsy. is component GATOR 1 complex, acting negative regulator mTOR signaling. Methods Zebrafish represents vertebrate model suitable for analysis drug screening epilepsy‐related...
Mutations of the leucine-rich glioma-inactivated 1 (LGI1) gene cause an autosomal dominant partial epilepsy with auditory features also known as autosomal-dominant lateral temporal lobe epilepsy. LGI1 is main antigen present in sera and cerebrospinal fluids patients limbic encephalitis seizures, highlighting its importance a spectrum epileptic disorders. encodes neuronal secreted protein, whose brain function still poorly understood. Here, we generated, by ENU (N-ethyl-N-nitrosourea)...
<h3>Objective:</h3> To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) subsequently search for additional mutations cohort of 107 families FS, or without epilepsy. <h3>Methods:</h3> The consisted 1 FS TLE, 64 smaller French recruited through national campaign, 43 Italian families. Molecular analyses whole-exome sequencing mutational screening. <h3>Results:</h3> Exome revealed p.Glu402fs*3 mutation γ2 subunit GABA<sub>A</sub> receptor...
Immunodeficient animals are valuable models for the engraftment of exogenous tissues; they widely used in many fields, including creation humanized animal models, as well regenerative medicine and oncology. Compared with mice, laboratory rats have a larger body size can more easily undergo transplantation various tissues organs. Considering absence high-quality resources immunodeficient rats, we CRISPR/Cas9 genome editing system to knock out interleukin-2 receptor gamma chain gene (Il2rg)...
Repeat expansion disorders, exemplified by myotonic dystrophy type 1 (DM1), present challenges in diagnostic quantification because of the variability and complexity repeat lengths. Traditional methods, including PCR Southern blotting, exhibit limitations sensitivity specificity, necessitating development innovative approaches for precise rapid diagnosis. Here, we introduce a CRISPR-based method, REPLICA (repeat-primed locating inherited disease Cas3), diagnosis DM1. This using...
The most frequent genetic cause of focal epilepsies is variations in the GAP activity toward RAGs 1 complex genes DEP domain containing 5 (DEPDC5), nitrogen permease regulator 2-like protein (NPRL2) and 3-like (NPRL3). Because these are associated with a broad spectrum epilepsies, unique pathology categorized as GATORopathy can be conceptualized. Animal models recapitulating clinical features patients essential to decipher GATORopathy. Although several genetically modified animal...
Humic substances are formed during the decomposition of organic matter in humus, and found many natural environments which materials microorganisms present. Oral administration humus extract to mice successfully induced effective protection against experimental challenge by two subspecies, Trypanosoma brucei T. gambiense. Mortality was most reduced among who received a 3% for 21 days drinking water ad libitum. Spleen cells from humus-administered exhibited significant non-specific cytotoxic...
Thioredoxin, encoded by Txn1, acts as a critical antioxidant in the defense against oxidative stress regulating dithiol/disulfide balance of interacting proteins. The role thioredoxin central nervous system (CNS) is largely unknown. A phenotype-driven study N-ethyl-N-nitrosourea-mutated rats with wild-running seizures revealed importance Txn1 mutations CNS degeneration. Genetic mapping identified Txn1-F54L epileptic rats. insulin-reducing activity was approximately one-third that wild-type...
Thioredoxin, encoded by Txn1, is a critical antioxidant that protects against oxidative damage regulating the dithiol/disulfide balance of interacting proteins. We recently discovered Adem rat, an epileptic rat harboring Txn1-F54L mutation, characterized wild running and vacuolar degeneration in midbrain. This study aimed to characterize classification epilepsy rats. performed simultaneous video-electroencephalographic recordings, magnetic resonance imaging, neurotransmitter measurements...
Hematopoietic stem cell (HSC) transplantation is extensively studied in mouse models, but their limited scale presents challenges for effective engraftment and comprehensive evaluations. Rats, due to larger size anatomical similarity humans, offer a promising alternative. In this study, we establish rat model with the KitV834M mutation, mirroring KitW41 mice often used KIT signaling HSC research. rats are viable fertile, displaying anemia mast depletion similar mice. The colony-forming unit...
The type I CRISPR system has recently emerged as a promising tool, especially for large-scale genomic modification, but its application to generate model animals by editing zygotes had not been established. In this study, we demonstrate genome in using the I-E CRISPR-Cas3 system, which efficiently generates deletions of several thousand base pairs at targeted loci mice with 40%–70% efficiency without off-target mutations. To overcome difficulties associated detecting variable deletions, used...
Epilepsy is one of the most frequent neurological disorders characterized by spontaneous and recurrent seizures. Most seizures last for lifetime patients require long term therapies. However, about 30% are refractory to antiepileptic drugs. Therefore, need newer more effective therapies urgent. Focal epilepsies, in which abnormal electrical discharges occur within neuronal networks limited hemisphere, accounts 60% all adult idiopathic epilepsy cases. Recently, mutations DEPDC5 gene has been...
Summary Hematopoietic stem cell (HSC) transplantation is extensively studied in mouse models, but their limited scale presents challenges for effective engraftment and comprehensive evaluations. Rats, due to larger size anatomical similarity humans, offer a promising alternative. In this study, we establish rat model with the Kit V834M mutation, mirroring W41 mice often used KIT signaling HSC research. rats are viable fertile, displaying anemia mast depletion similar mice. The mutation...