Journal article

Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice

Bradley J Turner, Neza Alfazema, Rebecca K Sheean, James N Sleigh, Kay E Davies, Malcolm K Horne, Kevin Talbot



Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spina..

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Awarded by Australian National Health & Medical Research Council

Awarded by Medical Research Council

Funding Acknowledgements

This work was supported by grants from the Australian National Health & Medical Research Council (Project Grant 1008910), MND Research Institute of Australia (Mick Rodger Benalla MND Research Grant), Bethlehem Griffiths Research Foundation Grant and Victorian Government through the Operational Infrastructure Scheme (BJT), Motor Neurone Disease Association (KT), and UK Medical Research Council (KED and JNS). The authors thank Prof Arthur Burghes for generously providing PrP-SMN mice, Dr Nicholas Parkinson, Dr Dirk Baumer, Fiona Christensen and Rian MacKenzie for mouse breeding and genotyping, Dr Tobias Merson for Iba1 antibody and Dr Julie Atkin for helpful discussions. Human spinal cord samples were received from Ms Fairlie Hinton, from the MND Research Tissue Bank of Victoria, supported by the Victorian Brain Bank Network, Mental Health Research Institute, Alfred Hospital, Victorian Forensic Institute of Medicine and the University of Melbourne. Studies were approved by the Howard Florey Institute Human and Animal Ethics Committees.