ArticleCell stem cell2015
Human Neuropsychiatric Disease Modeling using Conditional Deletion Reveals Synaptic Transmission Defects Caused by Heterozygous Mutations in NRXN1.
Article in Cell stem cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.
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Who cites it
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review.Journal of neurodevelopmental disorders · 2025Pooled it
- Gestational Hypoxia Disrupts Medial Ganglionic Eminence Progenitor Dynamics and Interneuron Development in Schizophrenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Distinct synaptic mechanisms underlie NRXN1 variant and disorder background-dependent phenotypes in iPSC-derived neurons.Cell reports · 2026Article
- Region-resolved proteomic map of the human brain: functional interconnections and neurological implications.Signal transduction and targeted therapy · 2026Article
- Probing neuropsychiatric disorders through in vivo CRISPR screening.Current opinion in genetics & development · 2026Review
- Generating and characterizing human telencephalic brain organoids from stem cell-derived single neural rosettes.Nature protocols · 2026Review
- Clinical Phenotypes Associated withSultan Qaboos University medical journal · 2026Article
- Patient-Derived Variants Define Constraints for Ligand Binding at the PDZ Domain of CASK.Journal of neurochemistry · 2025Article
- Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions.Journal of neurodevelopmental disorders · 2025Article
- Targeted splicing approach for alleviation of a neurexin 1 haploinsufficiency model.Molecular psychiatry · 2025Article
- Distinct Synaptic Mechanisms DrivebioRxiv : the preprint server for biology · 2025Article
- Rare Copy Number Variants Reveal Critical Cell Types and Periods of Brain Development in Neurodevelopmental Disorders.Biological psychiatry global open science · 2025Article
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- Alpha-neurexins in health and disease.Frontiers in molecular neuroscience · 2025Review
- A fast and responsive voltage indicator with enhanced sensitivity for unitary synaptic events.Neuron · 2024Article
- Efficient Gene-Editing in Human Pluripotent Stem Cells Through Simplified Assembly of Adeno-Associated Viral (AAV) Donor Templates.Bio-protocol · 2024Article
- Probing the molecular and cellular pathological mechanisms of schizophrenia using human induced pluripotent stem cell models.Schizophrenia research · 2024Review
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism.Molecular psychiatry · 2024Article
84 more citing papers are in PubMed but not listed here.
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9 authors at 2 institutions in 1 country.
Funding
Abstract
Heterozygous mutations of the NRXN1 gene, which encodes the presynaptic cell-adhesion molecule neurexin-1, were repeatedly associated with autism and schizophrenia. However, diverse clinical presentations of NRXN1 mutations in patients raise the question of whether heterozygous NRXN1 mutations alone directly impair synaptic function. To address this question under conditions that precisely control for genetic background, we generated human ESCs with different heterozygous conditional NRXN1 mutations and analyzed two different types of isogenic control and NRXN1 mutant neurons derived from these ESCs. Both heterozygous NRXN1 mutations selectively impaired neurotransmitter release in human neurons without changing neuronal differentiation or synapse formation. Moreover, both NRXN1 mutations increased the levels of CASK, a critical synaptic scaffolding protein that binds to neurexin-1. Our results show that, unexpectedly, heterozygous inactivation of NRXN1 directly impairs synaptic function in human neurons, and they illustrate the value of this conditional deletion approach for studying the functional effects of disease-associated mutations.
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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.