title: Characterization of genetic loss-of-function of Fus in zebrafish.
abstract: The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3'UTR usage, which could mask the effects of loss of Fus. Unlike published fus morphants, maternal zygotic fus mutants do not show motoneuronal degeneration and exhibit normal locomotor activity.
authors.affiliation: a Institute of Molecular Biology , Mainz , Germany.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lebedeva
authors.affiliation: a Institute of Molecular Biology , Mainz , Germany.
authors.forename: António M
authors.initials: AM
authors.lastname: de Jesus Domingues
authors.affiliation: a Institute of Molecular Biology , Mainz , Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Butter
authors.affiliation: a Institute of Molecular Biology , Mainz , Germany.
authors.forename: René F
authors.initials: RF
authors.lastname: Ketting
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D064113:CRISPR-Cas Systems; D005091:Exons; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D000068617:Genetic Background; D005838:Genotype; D020543:Proteome; D000094704:RNA, Guide, CRISPR-Cas Systems; D034702:RNA-Binding Protein FUS / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020543:Proteome; D000094704:RNA, Guide, CRISPR-Cas Systems; D034702:RNA-Binding Protein FUS
keywords: CRISPR-Cas9; Danio rerio; Fus; genetic knockout; morpholino; zebrafish