Since the discovery of the first gene to cause inherited (familial) amyotrophic lateral sclerosis (ALS) in 1993, there has been a boom in ALS gene discovery due to massive technological advances and reduction in costs in genomic sequencing. We can now easily read a person’s genetic code in a short amount of time for under $2000.
In 2014, Johnson and colleagues discovered ALS gene Matrin 3. They found three different mutations in Matrin-3 that are associated with both sporadic (not inherited) and familial ALS. Another Matrin 3 mutation is tied to a similar neuromuscular disease, called distal myopathy. Distal myopathy manifests in muscle weakness and atrophy of the upper and lower distal muscles, like muscles in the hands and feet.
Little is known about the normal function of the Matrin 3 protein (MATR3) or why different mutations in Matrin 3 can cause ALS and distal myopathy. With this in mind, Drs. Jada Lewis and David Borchelt from the University of Florida in Gainesville set out to determine the role of Matrin-3 in these diseases. They started by creating mouse models expressing the human wildtype (non-mutated) Matrin-3. The mice developed muscle weakness or paralysis over time in the hindlimbs, as well as muscle atrophy in the hindlimbs and forelimbs. These characteristics point to a role for Matrin 3 in neuromuscular function.
The ALS Association is proud to support Drs. Lewis and Borchelt in their studies to develop the first mouse models of ALS gene Matrin 3. This is one of the first steps to understand the function of Matrin 3 progress out of the University of Florida!
Moloney C, Rayapolu S, Howard J, Fromholt S, Brown H, Collins M, Cabrera M, Duffy C, Siemienski Z, Miller D, Swanson MS, Notterpek L, Borchelt DR, Lewis J. Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype. Acta Neuropathol Commun. 2016 Nov 18. [PUBMED].