Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis

Owen M. Peters, Elizabeth A. Lewis, Jeannette M. Osterloh, Alexandra Weiss, Johnny S. Salameh, Jake Metterville, Robert H. Brown, Marc Freeman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Axon degeneration occurs in all neurodegenerative diseases, but the molecular pathways regulating axon destruction during neurodegeneration are poorly understood. Sterile Alpha and TIR Motif Containing 1 (Sarm1) is an essential component of the prodegenerative pathway driving axon degeneration after axotomy and represents an appealing target for therapeutic intervention in neurological conditions involving axon loss. Amyotrophic lateral sclerosis (ALS) is characterized by rapid, progressive motor neuron degeneration and muscle atrophy, causing paralysis and death. Patient tissue and animal models of ALS show destruction of upper and lower motor neuron cell bodies and loss of their associated axons. Here, we investigate whether loss of Sarm1 can mitigate motor neuron degeneration in the SOD1G93A mouse model of ALS. We found no change in survival, behavioral, electrophysiogical or histopathological outcomes in SOD1G93A mice null for Sarm1. Blocking Sarm1-mediated axon destruction alone is therefore not sufficient to suppress SOD1G93A-induced neurodegeneration. Our data suggest the molecular pathways driving axon loss in ALS may be Sarm1-independent or involve genetic pathways that act in a redundant fashion with Sarm1.

Original languageEnglish (US)
Pages (from-to)3761-3771
Number of pages11
JournalHuman Molecular Genetics
Volume27
Issue number21
DOIs
StatePublished - Nov 1 2018

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Nerve Degeneration
Amyotrophic Lateral Sclerosis
Motor Neurons
Axons
Axotomy
Muscular Atrophy
Paralysis
Neurodegenerative Diseases
Animal Models
Survival

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis. / Peters, Owen M.; Lewis, Elizabeth A.; Osterloh, Jeannette M.; Weiss, Alexandra; Salameh, Johnny S.; Metterville, Jake; Brown, Robert H.; Freeman, Marc.

In: Human Molecular Genetics, Vol. 27, No. 21, 01.11.2018, p. 3761-3771.

Research output: Contribution to journalArticle

Peters, OM, Lewis, EA, Osterloh, JM, Weiss, A, Salameh, JS, Metterville, J, Brown, RH & Freeman, M 2018, 'Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis', Human Molecular Genetics, vol. 27, no. 21, pp. 3761-3771. https://doi.org/10.1093/hmg/ddy260
Peters, Owen M. ; Lewis, Elizabeth A. ; Osterloh, Jeannette M. ; Weiss, Alexandra ; Salameh, Johnny S. ; Metterville, Jake ; Brown, Robert H. ; Freeman, Marc. / Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis. In: Human Molecular Genetics. 2018 ; Vol. 27, No. 21. pp. 3761-3771.
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