Freezing activity brief data from a new FUS mutant zebrafish line.

The data presented in this paper are related to the research article "Functional characterization of a FUS mutant zebrafish line as a novel genetic model for ALS". In this model the lack of fus causes reduced lifespan as well as impaired motor abilities associated with a decrease of motor neurons axons lenght and an increase of neuromuscular junctions fragmentation. Data in this article describes the global locomotor activity data at 3, 4 and 5 days post fertilization in WT, fus heterozygous (fus+/-) and fus homozygous (fus-/-) zebrafish embryos as a response to visual light stimulation, with particular attention on the freezing respose.

Functional characterization of a FUS mutant zebrafish line as a novel genetic model for ALS.

Mutations in Fused in sarcoma (FUS), an RNA-binding protein, are known to cause Amyotrophic Lateral Sclerosis (ALS). However, molecular mechanisms due to loss of FUS function remain unclear and controversial. Here, we report the characterization and phenotypic analysis of a deletion mutant of the unique FUS orthologue in zebrafish where Fus protein levels are depleted. The homozygous mutants displayed a reduced lifespan as well as impaired motor abilities associated with specific cellular deficits, including decreased motor neurons length and neuromuscular junctions (NMJ) fragmentation. Furthermore, we demonstrate that these cellular impairments are linked to the misregulation of mRNA expression of acetylcholine receptor (AChR) subunits and histone deacetylase 4, markers of denervation and reinnervation processes observed in ALS patients. In addition, fus loss of function alters tau transcripts favoring the expression of small tau isoforms. Overall, this new animal model extends our knowledge on FUS and supports the relevance of FUS loss of function in ALS physiopathology.

Diagnostic Challenge and Neuromuscular Junction Contribution to ALS Pathogenesis.

Amyotrophic lateral sclerosis (ALS) represents the major adult-onset motor neuron disease. Both human and animal studies reveal the critical implication of muscle and neuromuscular junctions (NMJs) in the initial phase of this disease. Despite the common efforts, ALS diagnosis remains particularly challenging since many other disorders can overlap yielding similar clinical phenotypic features. A combination of further research on the NMJ parameters that are specific for this disease and laboratory tests are crucial for the early determination of specific changes in the muscle, as well as in motor neuron and the prediction of ALS progression. Also, it could provide a powerful tool in the discrimination of particular ALS and ALS-mimic cases and increase the efficacy of therapeutic treatments.