Assessing disease onset and progression in the SOD1 mouse model of ALS

&NA; SOD1 transgenic mice are the most widely used animal model of amyotrophic lateral sclerosis (ALS). In addition to providing valuable insights into the pathogenesis of ALS, these animals are used intensively in many laboratories as an in vivomodel for investigating novel therapeutic interventions towards this devastating motorneuron disease. Such pre‐clinical studies require objective and reliable quantification of the clinical phenotype of individual mice, most importantly of the neuromuscular abnormalities. Here we compare four parameters of the clinical phenotype: motor signs, body weight, rotarod performance and paw grip endurance for their usefulness in monitoring the SOD1 mouse model. We found that paw grip endurance is a sensitive and inexpensive alternative to the widely used rotarod test.

[1]  N. Shibata Transgenic mouse model for familial amyotrophic lateral sclerosis with superoxide dismutase‐1 mutation , 2001, Neuropathology : official journal of the Japanese Society of Neuropathology.

[2]  M. Gurney,et al.  A low expressor line of transgenic mice carrying a mutant human Cu,Zn superoxide dismutase (SOD1) gene develops pathological changes that most closely resemble those in human amyotrophic lateral sclerosis , 1997, Acta Neuropathologica.

[3]  D. Sanger,et al.  Quantitative motor assessment in FALS mice: a longitudinal study , 1997, Neuroreport.

[4]  J. Aitchison,et al.  Decision-Making in Clinical Medicine , 1970, Journal of the Royal College of Physicians of London.

[5]  Xiao-Hua Zhou,et al.  Statistical Methods in Diagnostic Medicine , 2002 .

[6]  J. Rothstein,et al.  Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS , 2002, Annals of neurology.

[7]  M. Gurney,et al.  Benefit of vitamin E, riluzole, and gababapentin in a transgenic model of familial amyotrophic lateral sclerosis , 1996, Annals of neurology.

[8]  J. Kong,et al.  Massive Mitochondrial Degeneration in Motor Neurons Triggers the Onset of Amyotrophic Lateral Sclerosis in Mice Expressing a Mutant SOD1 , 1998, The Journal of Neuroscience.

[9]  J. Julien,et al.  Pathways to motor neuron degeneration in transgenic mouse models. , 2002, Biochimie.

[10]  Michael P. McDonald,et al.  Mice lacking both subunits of lysosomal β–hexosaminidase display gangliosidosis and mucopolysaccharidosis , 1996, Nature Genetics.

[11]  M. Gurney,et al.  Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. , 1994, Science.

[12]  Ole A. Andreassen,et al.  Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis , 1999, Nature Medicine.