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Jul 16

Research Bit: Mice with human FUS, SOD1, TDP-43, C9orf72 genes to model ALS

Research Bits
The Packard Center welcomed Elizabeth Fisher, PhD from University College London to a recent Investigator's meeting.

Date: July 16, 2021

Presenter: Elizabeth Fisher, PhD

Talk Title: Mice with human FUS, SOD1, TDP-43, C9orf72 genes to model ALS

What was the question being asked?

How can we develop mouse models that more closely demonstrate human biology to understand the progression of disease?

Why is this important for ALS research?

One of the main drawbacks of using mouse models to study a disease is that the genes in mice are frequently not identical to those in humans. Dr. Fisher’s group aims to overcome this obstacle by replacing mouse genes with their human homologs. In other words, she is taking those genes that are associated with ALS in humans (such as FUS, TARDBP, SOD1, and C9ORF72) and putting them into mice. This seemingly simple approach is much more complex than it seems, as it requires extensive work to make sure that the replacement genes are working the way they should.

What was the take-home message?

Dr. Fisher’s group successfully replaced the FUS, TARDBP, SOD1 and C9ORF72 genes in mice, and has begun to characterize them as effective models for ALS. For the most part, replacement of the functional genes has not led to any observed alterations in the health of these mice. This is a significant step forward to have “humanized” mouse models to study ALS.

How do you think the results of this study might impact future approaches to the treatment of ALS?

With multiple humanized mouse models now characterized, Dr. Fisher and her group are interested in sharing these models with researchers around the world to begin studying how mutations in these ALS-associated genes contribute to motor neuron death. This advancement will certainly lead to more reproducible experiments in mice that can closely recapitulate the neurodegeneration that takes place in patients with ALS. Additionally, we are hopeful that these models will lead to better identification of drugs that are effective at treating ALS.

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