A new study recently published in the journal Acta Neuropathologica Communications revealed that the absence of the FUS/TLS protein, which has been linked to neurological diseases, causes symptoms distinct from the ones found in amyotrophic lateral sclerosis (ALS) patients. The study is entitled “FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis” and was led by researchers in Japan at Juntendo University Graduate School of Medicine, Core Research for Evolutionary Science and Technology (CREST) and RIKEN Brain Science Institute.
Mutations in a gene known to regulate RNA metabolism, the RNA-binding protein FUS/TLS gene (fused in sarcoma/translocated in sarcoma), have been associated with neurological diseases, namely ALS. ALS is a progressive neurodegenerative disease characterized by the gradual degeneration and atrophy of motor neurons in the brain and spinal cord that are responsible for controlling voluntary muscles, such as ones related to movement, speaking, eating, and even breathing. ALS patients may become totally paralyzed and the majority die due to respiratory failure.
It is not clear whether ALS pathogenesis is linked to a gain or loss of function of FUS/TLS. In this study, the research team established a viable mouse model lacking FUS/TLS in order to determine the in vivo effects of FUS/TLS depletion in the central nervous system and the possible link to ALS.
Researchers found that adult mice lacking FUS/TLS have anomalies in terms of behavior and brain structure that are not related to ALS symptoms or phenotype, suggesting that the loss of FUS/TLS function is not enough to cause ALS. These animals exhibited hyperactivity, reduced anxiety-like behavior and vacuole-like structures in the brain hippocampus. Alterations in gene expression and at the RNA level (transcriptome) of more than 100 genes, mainly linked to the central nervous system, were also found in mice lacking FUS/TLS, where two specific RNA molecules, Taf15 (a homologue of FUS/TLS) and Hnrnpa1 (an RNA-binding protein that has been implicated in ALS), were found to be upregulated.
The research team concluded that FUS/TLS depletion causes alterations in RNA metabolism leading to behavioral and pathological abnormalities that might be important to neurodegenerative conditions, but not to ALS.