Centre d'Information et de documentation du CRA Rhône-Alpes
CRA
Informations pratiques
-
Adresse
Centre d'information et de documentation
du CRA Rhône-Alpes
Centre Hospitalier le Vinatier
bât 211
95, Bd Pinel
69678 Bron CedexHoraires
Lundi au Vendredi
9h00-12h00 13h30-16h00Contact
Tél: +33(0)4 37 91 54 65
Mail
Fax: +33(0)4 37 91 54 37
-
Détail de l'auteur
Auteur J. LIN |
Documents disponibles écrits par cet auteur (1)
Faire une suggestion Affiner la recherche
CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors / C. X. LIU in Molecular Autism, 9 (2018)
[article]
Titre : CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors Type de document : Texte imprimé et/ou numérique Auteurs : C. X. LIU, Auteur ; C. Y. LI, Auteur ; C. C. HU, Auteur ; Y. WANG, Auteur ; J. LIN, Auteur ; Y. H. JIANG, Auteur ; Q. LI, Auteur ; X. XU, Auteur Article en page(s) : 23p. Langues : Anglais (eng) Mots-clés : Asd Animal model CRISPR/Cas9 Social behavior Zebrafish shank3 Index. décimale : PER Périodiques Résumé : Background: Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b. Previous studies have reported shank3 morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of shank3b mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique. Methods: CRISPR/Cas9 was applied to generate a shank3b loss-of-function mutation (shank3b(-/-) ) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in shank3b mutant zebrafish. Results: shank3b(-/-) zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of shank3b-deficient zebrafish. Conclusions: We generated the first inheritable shank3b mutant zebrafish model using CRISPR/Cas9 gene editing approach. shank3b(-/-) zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human SHANK3 function and ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0204-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354
in Molecular Autism > 9 (2018) . - 23p.[article] CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors [Texte imprimé et/ou numérique] / C. X. LIU, Auteur ; C. Y. LI, Auteur ; C. C. HU, Auteur ; Y. WANG, Auteur ; J. LIN, Auteur ; Y. H. JIANG, Auteur ; Q. LI, Auteur ; X. XU, Auteur . - 23p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 23p.
Mots-clés : Asd Animal model CRISPR/Cas9 Social behavior Zebrafish shank3 Index. décimale : PER Périodiques Résumé : Background: Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b. Previous studies have reported shank3 morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of shank3b mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique. Methods: CRISPR/Cas9 was applied to generate a shank3b loss-of-function mutation (shank3b(-/-) ) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in shank3b mutant zebrafish. Results: shank3b(-/-) zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of shank3b-deficient zebrafish. Conclusions: We generated the first inheritable shank3b mutant zebrafish model using CRISPR/Cas9 gene editing approach. shank3b(-/-) zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human SHANK3 function and ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0204-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354