Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1-mutant neurons

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 22; pp. 1 - 12
• Main Authors: Pak, ChangHui, Danko, Tamas, Mirabella, Vincent R., Wang, Jinzhao, Liu, Yingfei, Vangipuram, Madhuri, Grieder, Sarah, Zhang, Xianglong, Ward, Thomas, Huang, Yu-Wen Alvin, Jin, Kang, Dexheimer, Philip, Bardes, Eric, Mitelpunkt, Alexis, Ma, Junyi, McLachlan, Michael, Moore, Jennifer C., Qu, Pingping, Purmann, Carolin, Dage, Jeffrey L., Swanson, Bradley J., Urban, Alexander E., Aronow, Bruce J., Pang, Zhiping P., Levinson, Douglas F., Wernig, Marius, Südhof, Thomas C.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01.06.2021
• Subjects: Biological Sciences; Calcium-Binding Proteins - genetics; Case-Control Studies; Cell Transdifferentiation; Cells, Cultured; Cohort Studies; Drug discovery; Embryo cells; Embryonic Stem Cells - cytology; Gene Expression; Guanylate Kinases - metabolism; Heterozygote; Humans; Impairment; Induced Pluripotent Stem Cells - cytology; Mental disorders; Mutation; Neural Cell Adhesion Molecules - genetics; Neurodevelopmental disorders; Neurogenesis; Neurons; Neurons - metabolism; Neurotransmitter Agents - metabolism; Neurotransmitter release; Neurotransmitters; Paired-pulse depression; Phenotypes; Pluripotency; Point mutation; Schizophrenia; Schizophrenia - metabolism; Stem cell transplantation; Stem cells; synaptic transmission; schizophrenia; NMDA receptor; synapse formation; neurexin

Heterozygous NRXN1 deletions constitute the most prevalent currently known single-gene mutation associated with schizophrenia, and additionally predispose to multiple other neurodevelopmental disorders. Engineered heterozygous NRXN1 deletions impaired neurotransmitter release in human neurons, sugge...