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Conditional truncation of the FUS protein in mice : a new animal model of the ALS/FTD continuum

Scekic-Zahirovic, Jelena. Conditional truncation of the FUS protein in mice : a new animal model of the ALS/FTD continuum. 2015, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12632

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Abstract

Amyotrophic lateral sclerosis (ALS) and Frontotemporal dementia (FTLD) are now considered
as a unique clinicopathological spectrum referred to as ALS/FTLD. Cytoplasmic aggregation of the
physiologically nuclear FUS protein is a hallmark feature of a subset of ALS/FTLD. It remains
unknonwn whether the critical pathogenic event relies on a loss of FUS normal nuclear functions, a
toxic gain of function of FUS in the cytoplasm, or a combination of both.
To answer this question we have generated a conditional mouse model expressing truncated
FUS without nuclear localization signal - FusΔNLS. Our data showed that complete cytoplasmic
mislocalization of truncated FUS protein within spinal motor neurons is a major determinant of motor
neuron degeneration via toxic gain of function. A partial mislocalization of truncated FUS protein was
sufficient to trigger key features of ALS and of FTLD.These studies allowed the elucidation of
mechanisms underlying FUS role in ALS/FTLD, and will hopefully lead to development of therapies
for these devastating diseases.
Advisors:Caroni, Pico and Dupuis, Luc and Bartos, Marlene
Faculties and Departments:05 Faculty of Science
09 Associated Institutions > Friedrich Miescher Institut FMI > Neurobiology > Plasticity of neuronal connections (Caroni)
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12632
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (verschiedene Seitenzählungen)
Language:English
Identification Number:
Last Modified:21 Jun 2018 08:44
Deposited On:21 Jun 2018 08:43

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