Dataset Information

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.

OTHER RELATED OMICS DATASETS IN: PRJNA338793

INSTRUMENT(S): Q Exactive

ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio)

TISSUE(S): Brain

SUBMITTER: F Butter

LAB HEAD: Falk Butter

PROVIDER: PXD004876 | Pride | 2018-06-15

REPOSITORIES: Pride

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			Action	DRS
	20141115_QEP1_FBU_FB_collab_Ketting_fus_zebrafish_ko_1.raw	Raw
	20141115_QEP1_FBU_FB_collab_Ketting_fus_zebrafish_ko_2.raw	Raw
	20141115_QEP1_FBU_FB_collab_Ketting_fus_zebrafish_ko_3.raw	Raw
	20141115_QEP1_FBU_FB_collab_Ketting_fus_zebrafish_ko_4.raw	Raw
	20141115_QEP1_FBU_FB_collab_Ketting_fus_zebrafish_wt_1.raw	Raw

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Characterization of genetic loss-of-function of Fus in zebrafish.

Lebedeva Svetlana S de Jesus Domingues António M AM Butter Falk F Ketting René F RF

RNA biology 20161129 1

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 ...[more]

PMID: 27898262

Similar Datasets

Project description:FUS is an RNA-binding protein involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS-containing aggregates are often associated with concomitant loss of nuclear FUS. Whether loss of nuclear FUS function, gain of a cytoplasmic function, or a combination of both lead to neurodegeneration remains elusive. To address this question, we generated knock-in mice expressing mislocalized cytoplasmic FUS and complete FUS knock-out mice. Both mouse models display similar perinatal lethality with respiratory insufficiency, reduced body weight and length, and largely similar alterations in gene expression and mRNA splicing patterns, indicating that mislocalized FUS results in loss of its normal function. However, FUS knock-in mice, but not FUS knock-out mice, display reduced motor neuron numbers at birth, associated with enhanced motor neuron apoptosis, which can be rescued by cell-specific CRE-mediated expression of wild-type FUS within motor neurons. Together, our findings indicate that cytoplasmic FUS mislocalization not only leads to nuclear loss of function, but also triggers motor neuron death through a toxic gain of function within motor neurons. Total RNA from brains of E18.5 knock-in (FusÎNLS/ÎNLS), and knock-out (Fus-/-) mice and their control littermates were extracted with Trizol and libraries were prepared for RNA sequencing and RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Generation sequencing (RASL-seq) (Li et al. 2012; Zhou et al. 2012). For the RNA-seq experiment, biological replicates were used with n=4-5 knock-in animals per group (4 wild-type and 5 homozygous FusÎNLS) and n=5 knock-out animals per group (5 wild-type and 5 homozygous Fus-/-). For the RASL-seq analysis, biological replicates were used with n=4 knock-in animals per group (4 wild-type, 4 heterozygous and 4 homozygous FusÎNLS) and n=5 animals per group (5 wild-type and 5 homozygous Fus-/- knock-out).