Newswise — A horde of mice that mimic ALS and frontotemporal dementia are helping scientists understand the diseases and test treatments. Some debuted at RNA Metabolism in Neurological Disease, a conference held October 15-16 in Chicago, while another was recently described in the journal Neuron.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia can both result from a DNA expansion in a gene on chromosome 9 called C9ORF72. This happens when repeat sequences of six DNA bases (GGGGCC) grow from a handful into hundreds or thousands of copies. ALS affects between 20,000 and 30,000 people in the United States, killing the nerve cells in their spines and causing paralysis and death within a few years. A similar number of people develop frontotemporal dementia, in which the nerve cells that control behaviors, personality, or language degenerate. It too is fatal, though the length of time before death varies. Sometimes these conditions co-exist, and they can be caused by the same genetic mutations, such as those in C9ORF72.
Scientists are trying to figure out if the RNAs containing those repeats, the proteins they encode, or the loss of the normal protein cause the disease. Based on the new mice, losing the normal gene does not cause neurological disease, suggesting the RNAs or proteins made by the C9ORF72 repeats are toxic.
Scientists engineered mice that make up to 1,000 repeats, either with a partial or complete C9ORF72 gene. The mice with the partial gene were pretty healthy. They moved around and behaved normally, and lived normal lifespans, even though they produced RNAs and proteins from the repeats. Only some of the mice with the full C9ORF72 gene plus repeats got sicker. These animals lost weight and had trouble moving, and many died early. Researchers are not sure why these mice had more severe disease. Other mice with the full gene and many repeats seemed unaffected, leaving scientist to surmise that some additional factors, such as age or environmental stresses, might conspire to cause ALS and FTD.
Other scientists made mice missing the C9ORF72 gene. These animals got pretty sick and died, but not necessarily from a disease like ALS or dementia. Rather, they had problems akin to the blood cancer lymphoma. Because their neurons appeared normal, scientists concluded that loss of the normal C9ORF72 protein is probably not what causes neurodegenerative disease in people.
Not only will the new mice help scientists understand ALS and frontotemporal dementia, scientists said, they should also provide a testing ground for treatments that prevent the C9ORF72 repeats from making RNAs or proteins.
Alzforum’s conference and research news on this topic are freely accessible.
About UsFounded in 1996, Alzforum is a news and information resource website dedicated to helping researchers accelerate discovery and advance development of diagnostics and treatments for Alzheimer’s disease and related disorders.
Our site expands the traditional mode of scientific communication by reporting the latest scientific findings and industry news with insightful analysis that puts breaking news into context. We advance research by developing open-access databases of curated, highly specific scientific content to visualize and facilitate the exploration of complex data. Alzforum is a platform to disseminate the evolving knowledge around basic, translational, and clinical research in the field of AD.
Alzforum is supported by a team with backgrounds in science, journalism, information technology, design, and data science. Together with a distinguished Scientific Advisory Board, and the active participation of a global network of scientists, we strive to produce unbiased content to a rigorous editorial standard.
Alzforum is operated by the Biomedical Research Forum (BRF) LLC. BRF is a wholly owned subsidiary of FMR LLC. FMR LLC and its affiliates invest broadly in many companies, including life sciences and pharmaceutical companies.Alzforum does not endorse any specific product or scientific approach.
RSS