Mayo Scientists Develop Mouse Model for ALS and FTD Associated with C9ORF72 Mutations

Scientists at the Mayo Clinic, Jacksonville, Florida, have created a novel mouse that exhibits the symptoms and neurodegeneration associated with the most common genetic forms of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), both of which can be caused by mutations in a gene called C9ORF72. The study was published online on May 14, 2015 in Science. The article is titled “C9ORF72 Repeat Expansions in Mice Cause TDP-43 Pathology, Neuronal Loss, and Behavioral Deficits.” More than 30,000 Americans live with ALS, which destroys nerves that control essential movements, including speaking, walking, breathing, and swallowing. After Alzheimer's disease, FTD is the most common form of early-onset dementia. It is characterized by changes in personality, behavior, and language due to loss of neurons in the brain's frontal and temporal lobes. Patients with mutations in the chromosome 9 open reading frame 72 (C9ORF72) gene have all or some symptoms associated with both disorders. "Our mouse model exhibits the pathologies and symptoms of ALS and FTD seen in patients with the C9ORF72 mutation," said the study's lead author, Leonard Petrucelli, Ph.D., Chair and Ralph and Ruth Abrams Professor of the Department of Neuroscience at the Mayo Clinic, and a senior author of the study. "These mice could greatly improve our understanding of ALS and FTD and hasten the development of effective treatments." To create the model, Ms. Jeannie Chew, a Mayo Clinic Graduate School student and member of Dr. Petrucelli's team, injected the brains of newborn mice with a disease-causing version of the C9ORF72 gene. As the mice aged, they became hyperactive, anxious, and antisocial, in addition to having problems with movement that mirrored ALS/FTD patient symptoms.
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