title: Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin.
abstract: The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP.
authors.affiliation: Department of Medical Genetics and Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Connell
authors.affiliation: Department of Medical Genetics and Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Allison
authors.affiliation: Department of Medical Genetics and Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Evan
authors.initials: E
authors.lastname: Reid
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005684:Gait / Q000502:physiology*; D055879:Gene Knock-In Techniques; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000503:physiopathology*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C498515:Spast protein, mouse