The ALS Association

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Carrie Munk
The ALS Association



New UBQLN2 ALS Mouse Model Replicates Many Key Disease Features

Washington, D.C. (November 9, 2016) — An ALS Association-funded research team led by Mervyn Monteiro, Ph.D., Professor at the University of Maryland School of Medicine in Baltimore, has developed a new mouse model that faithfully replicates many aspects of the disease, including the formation of characteristic aggregates of an ALS-linked protein called TDP-43. The new model was created by inserting a mutant ubiquilin 2 (UBQLN2) gene, an important contributor to protein recycling, according to a new study published this week in the Proceedings of the National Academy of Sciences. The new model will help decipher how mutations in UBQLN2 cause ALS in people, and more generally how defects in protein recycling contribute to neurodegeneration.

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which leads to total paralysis and death, usually within two to five years of diagnosis. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure, and only one drug approved by the U.S. Food and Drug Administration (FDA) modestly extends survival.

UBQLN2 acts as a shuttle, ferrying misfolded proteins to the cell’s protein recycling machinery. Mutations in UBQLN2 were discovered in 2011 as a rare cause of ALS-frontotemporal dementia (FTD), a related neurodegenerative disease. In the new study, Dr. Monteiro and the three primary co-authors Nhat Le, Ph.D., Lydia Chang, Ph.D. and Irina Kovlyagina, Ph.D. inserted the mutant UBQLN2 gene into mice. The mice developed progressive muscle weakness and paralysis, as well as memory deficits. Analysis of brain and spinal cord tissue showed the development of characteristic protein aggregates similar to those seen in human disease, including aggregates containing TDP-43, which are common to almost all forms of ALS.

“This new mouse model is an excellent tool that mimics many of the components of ALS,” said ALS Association Chief Scientist Lucie Bruijn, Ph.D., M.B.A., “and in combination with other models, is likely to help us develop new therapies.”

Because this mouse model develops TDP-43 aggregates, it may be especially important for determining whether and how these widespread protein inclusions contribute to disease. This information should be directly useful for deciding whether to target TDP-43 aggregates in treatment development.

About The ALS Association
The ALS Association is the only national non-profit organization fighting Lou Gehrig’s Disease on every front.  By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships, The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure.  For more information about The ALS Association, visit our website at

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