title: Significance of behavioural tests in a transgenic mouse model of amyotrophic lateral sclerosis (ALS).
abstract: Amyotrophic Lateral Sclerosis (ALS) is a devastating adult-onset motor neuron disorder with marginal therapeutic options. The disease is characterized by progressive degeneration of motor neurons in spinal cord and motor cortex. Transgenic mice carrying the G93A mutation of the superoxide dismutase 1 (SOD1) gene develop a neurodegenerative disease closely mimicking human ALS. Several methods are currently used to record disease onset and progression of the animals in preclinical studies. For the interpretation of these preclinical trials, it is important to assess neurological function as sensitively as possible. In the present study, five different parameters (rotarod performance, weight, footprint analysis for both step length and runtime and the general condition of the mice scored from 1 to 5) were compared with respect to their significance to detect symptom onset and to monitor disease progression in transgenic G93A ALS mice. The rotarod and footprint analyses were performed weekly while the weight was recorded up to three times a week at later time points. General condition was assessed daily. First deficits were detected by rotarod testing and step length analyses. General condition score and weight showed first changes two weeks later. For preclinical testing of novel drug treatments rotarod and footprint analysis for step length therefore seem to be the most effective methods to detect symptom onset and potential treatment induced improvements.
authors.affiliation: Hannover Medical School, Department of Neurology, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. Knippenberg.sarah@mh-hannover.de
authors.forename: Sarah
authors.initials: S
authors.lastname: Knippenberg
authors.forename: Nadine
authors.initials: N
authors.lastname: Thau
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D004185:Disability Evaluation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005684:Gait; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D009483:Neuropsychological Tests; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013997:Time Factors
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1