title: Disease progression of human SOD1 (G93A) transgenic ALS model rats.
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.
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Arifumi
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamichi
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
authors.forename: Makiko
authors.initials: M
authors.lastname: Nagai
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000375:Aging / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight / Q000502:physiology; D002452:Cell Count; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008124:Locomotion / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000473:pathology; D015588:Observer Variation; D004856:Postural Balance / Q000502:physiology; D051381:Rats; D012018:Reflex / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1