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Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish
KATNAL2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders (NDDs) such as intellectual disability (ID) in several cohorts. KATNAL2 has been implicated in brain development, as it is required for ciliogenesis in Xenopus and is required fo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368773/ https://www.ncbi.nlm.nih.gov/pubmed/35955524 http://dx.doi.org/10.3390/ijms23158389 |
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author | Zheng, Jing Long, Fei Cao, Xu Xiong, Bo Li, Yu |
author_facet | Zheng, Jing Long, Fei Cao, Xu Xiong, Bo Li, Yu |
author_sort | Zheng, Jing |
collection | PubMed |
description | KATNAL2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders (NDDs) such as intellectual disability (ID) in several cohorts. KATNAL2 has been implicated in brain development, as it is required for ciliogenesis in Xenopus and is required for dendritic arborization in mice. However, a causative relationship between the disruption of Katnal2 function and behavioral defects has not been established. Here, we generated a katnal2 null allele in zebrafish using CRISPR/Cas9-mediated genome editing and carried out morphological and behavioral characterizations. We observed that katnal2(-/-) embryos displayed delayed embryonic development especially during the convergence and extension (CE) movement. The hatched larvae showed reduced brain size and body length. In the behavioral tests, the katnal2(-/-) zebrafish exhibited reduced locomotor activity both in larvae and adults; increased nocturnal waking activity in larvae; and enhanced anxiety-like behavior, impaired social interaction, and reduced social cohesion in adults. These findings indicate an important role for katnal2 in development and behavior, providing an in vivo model to study the mechanisms underlying the ASD related to KATNAL2 mutations. |
format | Online Article Text |
id | pubmed-9368773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93687732022-08-12 Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish Zheng, Jing Long, Fei Cao, Xu Xiong, Bo Li, Yu Int J Mol Sci Article KATNAL2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders (NDDs) such as intellectual disability (ID) in several cohorts. KATNAL2 has been implicated in brain development, as it is required for ciliogenesis in Xenopus and is required for dendritic arborization in mice. However, a causative relationship between the disruption of Katnal2 function and behavioral defects has not been established. Here, we generated a katnal2 null allele in zebrafish using CRISPR/Cas9-mediated genome editing and carried out morphological and behavioral characterizations. We observed that katnal2(-/-) embryos displayed delayed embryonic development especially during the convergence and extension (CE) movement. The hatched larvae showed reduced brain size and body length. In the behavioral tests, the katnal2(-/-) zebrafish exhibited reduced locomotor activity both in larvae and adults; increased nocturnal waking activity in larvae; and enhanced anxiety-like behavior, impaired social interaction, and reduced social cohesion in adults. These findings indicate an important role for katnal2 in development and behavior, providing an in vivo model to study the mechanisms underlying the ASD related to KATNAL2 mutations. MDPI 2022-07-29 /pmc/articles/PMC9368773/ /pubmed/35955524 http://dx.doi.org/10.3390/ijms23158389 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zheng, Jing Long, Fei Cao, Xu Xiong, Bo Li, Yu Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish |
title | Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish |
title_full | Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish |
title_fullStr | Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish |
title_full_unstemmed | Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish |
title_short | Knockout of Katnal2 Leads to Autism-like Behaviors and Developmental Delay in Zebrafish |
title_sort | knockout of katnal2 leads to autism-like behaviors and developmental delay in zebrafish |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368773/ https://www.ncbi.nlm.nih.gov/pubmed/35955524 http://dx.doi.org/10.3390/ijms23158389 |
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