Brain-region-specific changes and dysregulation of activity regulated genes in Gria3 mutant mice, a genetic animal model of schizophrenia DOI Open Access
Wei-Chao Huang, Ryan J. Kast, Kira A. Perzel Mandell

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 17, 2024

ABSTRACT Protein-truncating variants in GRIA3 (encoding the GluA3/GluR3 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors) are associated with substantially increased risk schizophrenia (SCZ). Here we characterized Gria3 mutant mice carrying a protein-truncating mutation that mimics SCZ-associated variant. Transcriptomic analysis revealed activity-regulated genes downregulated cortical regions, while immune and glia-related pathways exhibit brain-region-specific changes. The transcriptomic changes remarkably different from those Grin2a mice, particularly prefrontal cortex, even though both encode receptors SCZ risk. Proteomic further demonstrated loss-of-function profoundly alters protein composition synapses. These findings genetic mouse model provide potential insights into pathophysiological mechanisms underlying SCZ.

Язык: Английский

Brain-region-specific changes and dysregulation of activity regulated genes in Gria3 mutant mice, a genetic animal model of schizophrenia DOI Open Access
Wei-Chao Huang, Ryan J. Kast, Kira A. Perzel Mandell

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 17, 2024

ABSTRACT Protein-truncating variants in GRIA3 (encoding the GluA3/GluR3 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors) are associated with substantially increased risk schizophrenia (SCZ). Here we characterized Gria3 mutant mice carrying a protein-truncating mutation that mimics SCZ-associated variant. Transcriptomic analysis revealed activity-regulated genes downregulated cortical regions, while immune and glia-related pathways exhibit brain-region-specific changes. The transcriptomic changes remarkably different from those Grin2a mice, particularly prefrontal cortex, even though both encode receptors SCZ risk. Proteomic further demonstrated loss-of-function profoundly alters protein composition synapses. These findings genetic mouse model provide potential insights into pathophysiological mechanisms underlying SCZ.

Язык: Английский

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