Disease progression of human SOD1 (G93A) transgenic ALS model rats

Arifumi Matsumoto, Yohei Okada, Masanori Nakamichi, Masaya Nakamura, Yoshiaki Toyama, Gen Sobue, Makiko Nagai, Masashi Aoki, Yasuto Itoyama, Hideyuki Okano

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies.

Original languageEnglish
Pages (from-to)119-133
Number of pages15
JournalJournal of neuroscience research
Volume83
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1

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Keywords

  • Amyotrophic lateral sclerosis
  • Behavioral analyses
  • Evaluation system
  • Phenotype
  • Variability

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Matsumoto, A., Okada, Y., Nakamichi, M., Nakamura, M., Toyama, Y., Sobue, G., Nagai, M., Aoki, M., Itoyama, Y., & Okano, H. (2006). Disease progression of human SOD1 (G93A) transgenic ALS model rats. Journal of neuroscience research, 83(1), 119-133. https://doi.org/10.1002/jnr.20708