TY  - GEN
T1  - A single copy transgenic mutant FUS strain reproduces age-dependent ALS phenotypes in C. elegans
AU  - Labarre, Audrey
AU  - Tossing, Gilles
AU  - Maios, Claudia
AU  - Doyle, James J
AU  - Parker, J Alex
DO  - 10.17912/micropub.biology.000473
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000473/
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal and incurable adult-onset neurodegenerative disease characterized by the progressive loss of motor neurons leading to muscular atrophy (Vucic et al., 2014). Despite the fact that the vast majority of ALS cases are sporadic, around 10% of patients have an inherited form of the disease (Renton et al., 2014). Among the genes known to be involved in familial cases of the disease, Fused in Sarcoma (FUS, also called TLS) is known to be accountable for aggressive and juvenile form of ALS (Conte et al., 2012; Shang & Huang, 2016). Our laboratory has previously generated multiple-copy transgenic animals expressing human wild-type and mutant full-length FUS which reproduced many aspects of the human disease (Vaccaro et al., 2012). However, advances in genetic manipulation have made it possible to generate single-copy transgenic C. elegans animals, which can be more accurate for investigating the mechanisms of human FUS-induced neuronal death since the transgenic expression levels resemble endogenous levels. Here, we present the characterization of the first single-copy transgenic human FUS nematodes. Animals expressing human mutant FUS (mFUS) recapitulate many aspects of the human disease, including adult-onset paralysis and motor neuron degeneration. Importantly, worms expressing single copy human wild-type FUS (wtFUS) do not display these phenotypes associated with the disease. Given the many advantages of small animal models in biomedical research, we believe this new model will be a powerful tool for future chemical suppression screening.
PY  - 2021
JO  - microPublication Biology
ER  -