Laboratory models of ALS help researchers understand the basic process of the disease, with an eye towards developing new therapies. The mainstay has been a mouse that bears the mutated human gene associated with familial ALS. A newer rodent model, an ALS rat, also is engineered to express human mutant SOD1. The rat is larger and surgery is easier for applications such as stem cell transplants. The worm, fish and the fly models of ALS will be especially valuable, and even cells growing in a dish are desirable as tools. Cell based tests that reflect the disease process in ALS can rapidly report on the potential of new molecules to serve as therapeutics.
A model system in biological research refers to anything that scientists use to recreate aspects of a disease or any biological process. A model can be a cell living in a dish. Or it can be a fly, or a fish. In ALS research, the mainstay has been a mouse that bears the human gene for the known mutation of SOD1 associated with familial ALS (see also Genetics of ALS, SOD1 and ALS).
Modern techniques of molecular biology allow researchers to manipulate genes with unprecedented ease. Scientists can boost the production of protein coded by a gene, or silence it. Mutation of the SOD1 gene can produce many aspects of ALS. That allows researchers to build models of the disease by inserting that gene into animals that are easy to study in the lab. The mouse bearing the human gene for mutant SOD1 was the first lab model clearly linked to ALS based on a known cause of the disease. But other models are now available or being designed. All will undoubtedly enable rapid progress in finding new ways to approach ALS treatment.
All models are merely tools, and each has certain advantages that lend power to the search for new ALS therapies. The SOD1 mouse is easily bred and housed in the lab. It has provided a large amount of data that other researchers can access. The newer rodent model, an ALS rat, also is engineered to express human mutant SOD1. The rat is larger and surgery is easier for applications such as stem cell transplants and other approaches that require injections into the spinal cord.
The worm and the fly models of ALS will be especially valuable as flies breed fast, and the worm has a basic and simple biology: it has 959 cells, and a three day life cycle. Genetics of both these creatures are known in great detail. The zebrafish model of ALS will also be a useful addition to the ALS research toolbox. Both the fish and the worm offer scientists the ability to actually watch what happens when proteins are changed by mutation, as the worm and the fish larvae both are transparent.
Even cells growing in a dish are desirable for ALS research. Cell based tests that reflect aspects of the disease process in ALS can rapidly report on the potential of new molecules to serve as therapeutics.
The ability of investigators to manipulate genes in animals that model human disease also leads to ways to ask, what other genes can influence the way a disease process appears or progresses. ALSA funded research is actively seeking other genes can influence the disease process in ALS.
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