A5021113518- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Amino Acid Enzymes and Metabolism
- Ubiquitin and proteasome pathways
- Neuroendocrine regulation and behavior
- Neurobiology and Insect Physiology Research
- Genetics and Physical Performance
- Genetics, Aging, and Longevity in Model Organisms
- Fetal and Pediatric Neurological Disorders
- RNA Research and Splicing
- Hippo pathway signaling and YAP/TAZ
- Animal Genetics and Reproduction
- Genetic Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Adipose Tissue and Metabolism
- Genomics and Chromatin Dynamics
- Neural dynamics and brain function
- Genomics and Rare Diseases
- Machine Learning in Healthcare
- Pancreatic function and diabetes
University of California, Berkeley
2025
Institute for Basic Science
2021-2024
Korea Advanced Institute of Science and Technology
2016-2020
ADNP syndrome, involving the transcription factor of SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). Although Adnp-haploinsufficient (Adnp-HT) mice display various phenotypic deficits, whether these abnormal synaptic functions remain poorly understood. Here, we report plasticity deficits associated with cognitive inflexibility CaMKIIα hyperactivity in Adnp-HT mice. These show impaired inflexible...
Abstract Background DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated mutations in the DLG2 promoter region are significantly associated autism spectrum disorder (ASD). Although well a schizophrenia-susceptibility gene, mechanisms link gene disruption ASD-like behaviors remain unclear. Methods Mice lacking exon 14 of Dlg2 (...
Abstract NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these impair social cognition behavior remains unclear. We report here that NMDARs cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv burst firing cognition. Shank2 –/– mice, displaying improved sociability upon NMDAR activation, show impaired representation inhibitory firing. Cortical neurons...
Shank3 is an excitatory postsynaptic scaffolding protein implicated in multiple brain disorders, including autism spectrum disorders and Phelan-McDermid syndrome. Although previous neurobiological studies on Shank3-mutant mice have revealed diverse roles of the regulation synaptic, neuronal, functions, whether expression specific cell types distinctly contributes to mouse phenotypes remains largely unclear. In present study, we generated two lines (exons 14–16) carrying global GABA...
Highlights•NGL-2 associates with and clusters NMDA receptors•NGL-2 deletion in mice suppresses synaptic NMDAR function•NGL-2 leads to autistic-like behaviors•Pharmacological activation improves behaviorsSummaryNetrin-G ligand 2 (NGL-2)/LRRC4, implicated autism spectrum disorders schizophrenia, is a leucine-rich repeat-containing postsynaptic adhesion molecule that interacts intracellularly the excitatory scaffolding protein PSD-95 trans-synaptically presynaptic netrin-G2. Functionally, NGL-2...
Shank3, an abundant excitatory postsynaptic scaffolding protein, has been associated with multiple brain disorders, including autism spectrum disorders and Phelan-McDermid syndrome. However, how cell type-specific Shank3 deletion affects disease-related neuronal functions remains largely unclear. Here we investigated the impacts of (exons 14–16) in glutamatergic neurons a dorsal telencephalic origin on synaptic behavioral phenotypes mice. Neuronal excitability was abnormally increased layer...
Shank3, a postsynaptic scaffolding protein involved in regulating excitatory synapse assembly and function, has been implicated several brain disorders, including autism spectrum disorders (ASD), Phelan-McDermid syndrome, schizophrenia, intellectual disability, mania. Here we generated characterized Shank3 knock-in mouse line carrying the Q321R mutation (Shank3Q321R mice) identified human individual with ASD that affects ankyrin repeat region (ARR) domain of protein. Homozygous...
Shank3 is an abundant excitatory postsynaptic scaffolding protein implicated in various neurodevelopmental disorders, including autism spectrum disorder (ASD), Phelan-McDermid syndrome, intellectual disability, and schizophrenia. -mutant mice show molecular, synaptic, behavioral deficits, but little known about how transcriptomic phenotypes vary across different ages, brain regions, gene dosages. Here, we report patterns the forebrains of juvenile adult homozygous that lack exons 14–16 also...
Gephyrin is a central scaffold protein that mediates development, function, and plasticity of mammalian inhibitory synapses by interacting with various synaptic proteins. Here, we show IQSEC3, guanine nucleotide exchange factor for ARF6, directly interacts gephyrin, an interaction critical the synapse localization IQSEC3. Overexpression IQSEC3 increases inhibitory, but not excitatory, density in activity-dependent manner. Conversely, knockdown decreases size gephyrin cluster without altering...
Abstract Tuberous Sclerosis Complex (TSC) is a genetic neurodevelopmental disorder associated with early onset epilepsy, intellectual disability and neuropsychiatric disorders. A hallmark of the cortical tubers, which are focal malformations brain development that contain dysplastic cells hyperactive mTORC1 signaling. One barrier to developing therapeutic approaches understanding origins tuber lack model system recapitulates this pathology. To address this, we established genetically mosaic...
Shank2 is an abundant excitatory postsynaptic scaffolding protein that has been implicated in various neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD), intellectual disability, attention-deficit/hyperactivity disorder, schizophrenia. Shank2-mutant mice show ASD-like behavioral deficits altered synaptic neuronal functions, but little known about how different brain regions gene dosages affect the transcriptomic phenotypes of these mice. Here, we performed...
Variants of the SH3 and multiple ankyrin repeat domains 3 ( SHANK3 ), which encodes postsynaptic scaffolds, are associated with brain disorders. The targeted alleles in a few Shank3 knock-out (KO) lines contain neomycin resistance (Neo) cassette, may perturb normal expression neighboring genes; however, this has not been investigated detail. We previously reported an unexpected increase mRNA exons 1–12 brains Shank3B KO mice generated by replacing 13–16 Neo cassette. In study, we confirmed...
Genetic variations resulting in the loss of function discs large homologs (DLG2)/postsynaptic density protein-93 (PSD-93) gene have been implicated increased risk for schizophrenia, intellectual disability, and autism spectrum disorders (ASDs). Previously, we reported that mice lacking exon 14 Dlg2 (Dlg2 -/- mice) display autistic-like behaviors, including social deficits repetitive as well suppressed spontaneous excitatory postsynaptic currents striatum. However, neural substrate...