Loss of function of the C9orf72 gene can affect communication between neurons and muscles

Amyotrophic lateral sclerosis, or ALS, attacks nerve cells known as motor neurons in the brain and spinal cord and gradually leads to paralysis. Loss of function of an important gene, C9orf72, can affect communication between motor neurons and muscles in people with the disease. The team led by Dr. Kessen Patten from the Institut national de la recherche scientifique (INRS) published in the renowned journal Communication biology.

A mutation in the C9orf72 gene is the primary genetic cause of ALS. The mutation in C9orf72 consists of a very unusual extension of a sequence of six DNA bases (GGGGCC) from a few copies (less than 20 in a healthy person) to over 1000 copies. The mutation, which sometimes leads to a loss of function, can be responsible for 40 to 50% of hereditary ALS cases and for 5 to 10% of cases without a family history.

Dr. Patten investigated the loss of function of this gene in genetically modified zebrafish models. In their work, led by PhD student Zoé Butti, the group found symptoms similar to ALS, namely motor disorders, muscle atrophy, loss of motor neurons, and mortality in individuals.

Synaptic transmission

The study showed how the loss of function induced by the mutation of the C9orf72 gene affects the communication between motor neurons and muscles. “This synaptic dysfunction is seen in all people with the disease and occurs before the motor neurons die,” noted the researcher and holder of the Anna Sforza Djoukhadjian Research Chair.

The research group also revealed the role of the gene on the protein TDP-43 (Transactive Response DNA Binding Protein 43), which plays an important role in ALS. The C9orf72 gene can influence the position of the TDP-43 protein within the cell. “In about 97% of ALS patients, the TDP-43 protein is used up from the nucleus and forms aggregates in the cytoplasm and not in the nucleus, as is the case in healthy people. We want to further investigate this relationship between the two proteins, ”explains Professor Patten.

Now that the team has developed a model, it will be able to test therapeutic molecules. The aim is to find a drug to restore the synaptic connection between neurons and muscles. It can also lead to a therapeutic goal to correct the abnormality in the TDP-43 protein.


About the study

The article “Reduced C9orf72 function leads to failure synaptic vesicle release and neuromuscular diagnostic in zebrafish” by Zoé Butti, Yingzhou Edward Pan and Shunmoogum A. Patten with the help of Dr. Jean Giacomotto of the Queensland Brain Institute was published in the journal Communication biology. The study received financial support from the ALS Society of Canada, the Brain Canada Foundation, the Anna Sforza Djoukhadjian Research Chair Fund, the Natural Sciences and Engineering Council of Canada, the Canada Foundation for Innovation, and the Canadian Institutes of Health Research.

About INRS

The INRS is a university devoted exclusively to research and education at the university level. Since its inception in 1969, the INRS has played an active role in the economic, social, and cultural development of Québec, and ranks first in Québec and Canada in terms of research intensity. INRS consists of four interdisciplinary research and training centers in Québec City, Montréal, Laval and Varennes with expertise in strategic sectors: Eau Terre Environnement, Énergie Matériaux Télécommunications, Urbanization Culture Société and Armand-Frappier Santé Biotechnologie. The INRS community includes more than 1,500 students, postdocs, faculty members, and staff.

Source :

Audrey-Maude Vezina

Service des Communications de l’INRS

418 254-2156

[email protected]


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