Disruption of grin2A, an Epilepsy-Associated Gene, Produces Altered Spontaneous Swim Behavior in Zebrafish

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00640235" target="_blank" >RIV/86652036:_____/25:00640235 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/25:00640235 RIV/00216208:11120/25:43928646 RIV/00216208:11310/25:10499866

Result on the web

<a href="https://doi.org/10.1523/JNEUROSCI.0946-25.2025" target="_blank" >https://doi.org/10.1523/JNEUROSCI.0946-25.2025</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1523/JNEUROSCI.0946-25.2025" target="_blank" >10.1523/JNEUROSCI.0946-25.2025</a>

Result language

angličtina

Original language name

Disruption of grin2A, an Epilepsy-Associated Gene, Produces Altered Spontaneous Swim Behavior in Zebrafish

Original language description

N-Methyl-d-aspartate receptors (NMDARs) control synaptic plasticity and brain development in a manner determined by receptor subunit composition. Pathogenic variants in GRIN2A gene, encoding the NMDAR GluN2A subunit, can cause gain or loss of function of receptors containing the affected subunit and are associated with intellectual disability and epilepsy in patients. While in vitro studies of recombinant receptors have yielded some insights, animal experimental models are essential to better understand the relationship between the molecular pathology of the variants and the disease. Here we introduce a zebrafish model of GluN2A loss of function to study system-level effects of zebrafish grin2Aa and grin2Ab gene deletion. Our electrophysiological analysis revealed functional differences between receptors containing zebrafish GluN2Aa/b and GluN2Bb paralogs comparable with mammalian receptors containing GluN2A versus GluN2B subunits. Both grin2Aa−/− and grin2Ab−/− as well as double-knock-out grin2A−/− zebrafish larvae showed increased locomotor activity in a novel environment. Proteomic analysis suggested that the relative proportion of GluN2B-containing NMDARs may be increased in grin2A mutant fish. Our results highlight fundamental similarities between zebrafish and mammalian NMDAR signaling and validate the use of zebrafish as a model organism to study the neurodevelopmental role of NMDARs. The newly created transgenic zebrafish strains complement the rodent models of GluN2A loss of function and can be used for high-throughput testing of pharmacological or genetic treatment strategies for patients with GRIN2A gene variants.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/GA23-04922S" target="_blank" >GA23-04922S: In vitro and in vivo study of the consequences of disease-associated mutations in the NMDA receptor and potential rescue pharmacology</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Neuroscience

ISSN

0270-6474

e-ISSN

1529-2401

Volume of the periodical

45

Issue of the periodical within the volume

33

Country of publishing house

US - UNITED STATES

Number of pages

17

Pages from-to

e0946252025

UT code for WoS article

001578101700005

EID of the result in the Scopus database

2-s2.0-105012995278