NDLI: ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function

Content Provider	PubMed Central
Author	Sharma, Aarti Lyashchenko, Alexander K. Lu, Lei Ebrahimi, Nasrabady Sara Elmaleh, Margot Mendelsohn, Monica Nemes, Adriana Tapia, Juan Carlos Mentis, George Z. Shneider, Neil A.
Copyright Year	2015
Abstract	Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations.
Related Links	http://dx.doi.org/10.1038/ncomms10465
Starting Page	10465
File Format	PDF
ISSN	20411723
e-ISSN	20411723
Journal	Nature Communications
Volume Number	7
Language	English
Publisher	Nature Publishing Group
Publisher Date	2016-02-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) Chemistry(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Chemistry Physics and Astronomy Biochemistry, Genetics and Molecular Biology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function

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