Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy

<p dir="ltr">We identified <i>N</i>-ethylmaleimide-sensitive factor attachment protein beta (NAPB) as a potential risk gene for autism and epilepsy. Notably, Qatari monozygotic triplets with loss of function mutations in <i>NAPB</i> exhibit early onset epilept...

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Main Author: Kyung Chul Shin (13913556) (author)
Other Authors: Waseem Hasan (17280670) (author), Gowher Ali (14152593) (author), Doua Abdelrahman (17280667) (author), Tala Abuarja (17075070) (author), Lawrence W. Stanton (6707191) (author), Sahar I. Da’as (9631717) (author), Yongsoo Park (761850) (author)
Published: 2025
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author Kyung Chul Shin (13913556)
author2 Waseem Hasan (17280670)
Gowher Ali (14152593)
Doua Abdelrahman (17280667)
Tala Abuarja (17075070)
Lawrence W. Stanton (6707191)
Sahar I. Da’as (9631717)
Yongsoo Park (761850)
author2_role author
author
author
author
author
author
author
author_facet Kyung Chul Shin (13913556)
Waseem Hasan (17280670)
Gowher Ali (14152593)
Doua Abdelrahman (17280667)
Tala Abuarja (17075070)
Lawrence W. Stanton (6707191)
Sahar I. Da’as (9631717)
Yongsoo Park (761850)
author_role author
dc.creator.none.fl_str_mv Kyung Chul Shin (13913556)
Waseem Hasan (17280670)
Gowher Ali (14152593)
Doua Abdelrahman (17280667)
Tala Abuarja (17075070)
Lawrence W. Stanton (6707191)
Sahar I. Da’as (9631717)
Yongsoo Park (761850)
dc.date.none.fl_str_mv 2025-04-29T09:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41598-025-96862-2
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Seizure-like_behavior_and_hyperactivity_in_i_napb_i_knockout_zebrafish_as_a_model_for_autism_and_epilepsy/30405625
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Neurosciences
Zebrafish
NAPB
Autism
SNARE
Microelectrode array (MEA)
dc.title.none.fl_str_mv Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">We identified <i>N</i>-ethylmaleimide-sensitive factor attachment protein beta (NAPB) as a potential risk gene for autism and epilepsy. Notably, Qatari monozygotic triplets with loss of function mutations in <i>NAPB</i> exhibit early onset epileptic encephalopathy and varying degrees of autism. In this study, we generated NAPB zebrafish model using CRISPR-Cas9-sgRNAs technology for gene editing of the two orthologs <i>napba </i>and <i>napbb</i>. We observed that napb crispants (CR) show shorter motor neuron axons length together with altered locomotion behavior, including significant increases in larvae total distance traveled, swimming velocity, and rotation frequency, indicating that these behavioral changes effectively mimic the human epileptic phenotype. We applied microelectrode array (MEA) technology to monitor neural activity and hyperactivity in the zebrafish model. The <i>napb</i> CR shows hyperexcitability in the brain region. By combining behavioral tests with electrophysiological MEA assays, the established NAPB zebrafish model can be employed to study the pathophysiological mechanisms of ASD and epilepsy to screen potential therapeutic drugs.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-025-96862-2" target="_blank">https://dx.doi.org/10.1038/s41598-025-96862-2</a></p>
eu_rights_str_mv openAccess
id Manara2_f2e06af1010289d64958f1b304e5d1f8
identifier_str_mv 10.1038/s41598-025-96862-2
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/30405625
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsyKyung Chul Shin (13913556)Waseem Hasan (17280670)Gowher Ali (14152593)Doua Abdelrahman (17280667)Tala Abuarja (17075070)Lawrence W. Stanton (6707191)Sahar I. Da’as (9631717)Yongsoo Park (761850)Biological sciencesGeneticsBiomedical and clinical sciencesNeurosciencesZebrafishNAPBAutismSNAREMicroelectrode array (MEA)<p dir="ltr">We identified <i>N</i>-ethylmaleimide-sensitive factor attachment protein beta (NAPB) as a potential risk gene for autism and epilepsy. Notably, Qatari monozygotic triplets with loss of function mutations in <i>NAPB</i> exhibit early onset epileptic encephalopathy and varying degrees of autism. In this study, we generated NAPB zebrafish model using CRISPR-Cas9-sgRNAs technology for gene editing of the two orthologs <i>napba </i>and <i>napbb</i>. We observed that napb crispants (CR) show shorter motor neuron axons length together with altered locomotion behavior, including significant increases in larvae total distance traveled, swimming velocity, and rotation frequency, indicating that these behavioral changes effectively mimic the human epileptic phenotype. We applied microelectrode array (MEA) technology to monitor neural activity and hyperactivity in the zebrafish model. The <i>napb</i> CR shows hyperexcitability in the brain region. By combining behavioral tests with electrophysiological MEA assays, the established NAPB zebrafish model can be employed to study the pathophysiological mechanisms of ASD and epilepsy to screen potential therapeutic drugs.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-025-96862-2" target="_blank">https://dx.doi.org/10.1038/s41598-025-96862-2</a></p>2025-04-29T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-025-96862-2https://figshare.com/articles/journal_contribution/Seizure-like_behavior_and_hyperactivity_in_i_napb_i_knockout_zebrafish_as_a_model_for_autism_and_epilepsy/30405625CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/304056252025-04-29T09:00:00Z
spellingShingle Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
Kyung Chul Shin (13913556)
Biological sciences
Genetics
Biomedical and clinical sciences
Neurosciences
Zebrafish
NAPB
Autism
SNARE
Microelectrode array (MEA)
status_str publishedVersion
title Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
title_full Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
title_fullStr Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
title_full_unstemmed Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
title_short Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
title_sort Seizure-like behavior and hyperactivity in <i>napb</i> knockout zebrafish as a model for autism and epilepsy
topic Biological sciences
Genetics
Biomedical and clinical sciences
Neurosciences
Zebrafish
NAPB
Autism
SNARE
Microelectrode array (MEA)