[article]
| Titre : |
Zebrafish frk Gene Knockout Shows Social Impairments Relevant to Autism and Delays Brain Development by Increasing Cell Proliferation |
| Type de document : |
texte imprimé |
| Auteurs : |
Xueting LIN, Auteur ; Jing WU, Auteur ; Yingchao YING, Auteur ; Binhong YAN, Auteur ; Jiangping WANG, Auteur ; Jian ZOU, Auteur ; Kewen JIANG, Auteur |
| Article en page(s) : |
p.e70310 |
| Langues : |
Anglais (eng) |
| Mots-clés : |
autism cell proliferation cyp24a1 fyn related kinase sociability tp53 zebrafish |
| Index. décimale : |
PER Périodiques |
| Résumé : |
ABSTRACT Fyn-related kinase (FRK), which belongs to the Src family of non-receptor protein tyrosine kinases, functions during the cell cycle. Here, we report an autistic patient with an intragenic mutation of FRK and two other autism-related genes. Circumventing the barrier of murine model studies, we generated the CRISPR/Cas9-engineered frk ?/? zebrafish. We found that frk-knockout led to early developmental abnormalities. Frk ?/? fish exhibited autism-like behavior, including impaired social communication, repetitive stereotypic behavior, altered anxiety level, and cognitive dysfunction in both larvae and adults, which could be rescued by the transgenic neuron-specific re-expression of frk. GO and KEGG analysis of RNA-sequencing data found that the frk-knockout-induced DEGs were mainly concentrated in processes and functions related to cell metabolism. PPI network analysis of the detected DEGs suggested that the cyp24a1/tp53 pathway may play a key role in frk-knockout-induced autism. Furthermore, we found that the numbers of BrdU+ cells were significantly increased in the frk ?/? larval brains. Inhibition of Cyp24a1 or activation of tp53 reduced cell proliferation and partially ameliorated social impairments in frk ?/? zebrafish. Overall, our work established an autism model of frk-knockout with an assessable behavior phenotype in zebrafish and provided key insights into cell proliferation and the influence of the cyp24a1/tp53 pathway-regulated cell proliferation on frk-knockout-induced autism-like behaviors. |
| En ligne : |
https://doi.org/10.1002/aur.70310 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=589 |
in Autism Research > 19-8 (August 2026) . - p.e70310
[article] Zebrafish frk Gene Knockout Shows Social Impairments Relevant to Autism and Delays Brain Development by Increasing Cell Proliferation [texte imprimé] / Xueting LIN, Auteur ; Jing WU, Auteur ; Yingchao YING, Auteur ; Binhong YAN, Auteur ; Jiangping WANG, Auteur ; Jian ZOU, Auteur ; Kewen JIANG, Auteur . - p.e70310. Langues : Anglais ( eng) in Autism Research > 19-8 (August 2026) . - p.e70310
| Mots-clés : |
autism cell proliferation cyp24a1 fyn related kinase sociability tp53 zebrafish |
| Index. décimale : |
PER Périodiques |
| Résumé : |
ABSTRACT Fyn-related kinase (FRK), which belongs to the Src family of non-receptor protein tyrosine kinases, functions during the cell cycle. Here, we report an autistic patient with an intragenic mutation of FRK and two other autism-related genes. Circumventing the barrier of murine model studies, we generated the CRISPR/Cas9-engineered frk ?/? zebrafish. We found that frk-knockout led to early developmental abnormalities. Frk ?/? fish exhibited autism-like behavior, including impaired social communication, repetitive stereotypic behavior, altered anxiety level, and cognitive dysfunction in both larvae and adults, which could be rescued by the transgenic neuron-specific re-expression of frk. GO and KEGG analysis of RNA-sequencing data found that the frk-knockout-induced DEGs were mainly concentrated in processes and functions related to cell metabolism. PPI network analysis of the detected DEGs suggested that the cyp24a1/tp53 pathway may play a key role in frk-knockout-induced autism. Furthermore, we found that the numbers of BrdU+ cells were significantly increased in the frk ?/? larval brains. Inhibition of Cyp24a1 or activation of tp53 reduced cell proliferation and partially ameliorated social impairments in frk ?/? zebrafish. Overall, our work established an autism model of frk-knockout with an assessable behavior phenotype in zebrafish and provided key insights into cell proliferation and the influence of the cyp24a1/tp53 pathway-regulated cell proliferation on frk-knockout-induced autism-like behaviors. |
| En ligne : |
https://doi.org/10.1002/aur.70310 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=589 |
|  |
Zebrafish frk Gene Knockout Shows Social Impairments Relevant to Autism and Delays Brain Development by Increasing Cell Proliferation in Autism Research, 19-8 (August 2026)
