Can zebrafish help us to learn more about MND?

A team at the Sheffield Institute for Translational Neuroscience are creating a zebrafish model to study the C9orf72 gene mutation in MND, and work out its role in the brain and spinal cord (our reference 864-792).

Zebrafish are a good way of modelling what happens in human MND. We know that many of the genes linked to causing MND in humans are also found in zebrafish. For example, changes to a gene called SOD-1 in humans are linked to about 20% of all cases of inherited MND, and when you genetically change the same gene in zebrafish they develop symptoms similar to MND.

A faulty or changed C9orf72 gene is associated with about 40% of all cases of the inherited form of MND. This change (or mutation) is also found in people with a form of dementia called frontotemporal dementia (FTD). FTD can alter abilities in decision-making and behaviour.

Zebrafish also have the C9orf72 gene. By removing or blocking this gene in the zebrafish, the researchers can figure out whether the fish develop symptoms similar to those found in MND. Knowing more about this gene in an animal model of MND will help in our understanding of how changes to the C9orf72 gene in people could contribute to MND.

Natalie’s PhD research

Natalie Rounding at symp

Natalie Rounding, presenting a Poster on her work at our International Symposium in 2015

PhD student Natalie Rounding, now in the third year of this project, has found that a change (mutation) of the C9orf72 gene in zebrafish gives rise to defects in the start of a process where the cell breaks down and recycles old or damaged proteins (known as autophagy).

Natalie is testing if the fish with the genetic change show problems with their movement. They can test this by observing how the fish swims.

A swim tunnel test shows if the fish with the gene mutation have problems with swimming endurance, by getting them to swim against a flow of water for a set time. Fish with the gene mutation show difficulties swimming for the whole amount time.

Interestingly, Natalie has found that zebrafish with the C9orf72 mutation have apparently normal motor function up to 12 months of age. Natalie is now looking at whether the fish show motor impairments later on in life; if they do then this would make sense as MND is a later-onset disease in humans.

Natalie has seen that fish with the C9orf72 mutation show changes in their behaviour from about 8 months of age. By putting the fish in a novel tank and seeing which area they spend more time in, she can see if the gene mutation is affecting their behaviour (such as anxiety). This may indicate if the fish are showing FTD-like symptoms.

For more information on funding research involving animals please see our website: www.mndassociation.org/animalresearch

Throughout June 2016 MND Awareness Month will be highlighting the rapid progression of the disease in its powerful Shortened Stories campaign, sharing the experiences of people currently living with MND, or who have lost loved ones to the disease, through art, poetry and film.

One thought on “Can zebrafish help us to learn more about MND?

  1. Thank you so much for this research! My Mum died from FTD with MND and it’s comforting to know there is research taking place to understand the diseases better.

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