Gait analysis detects early changes in transgenic SOD1(G93A) mice
Christine M. Wooley BS
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorRoger B. Sher PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorWayne N. Frankel PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorGregory A. Cox PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorCorresponding Author
Kevin L. Seburn PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USASearch for more papers by this authorChristine M. Wooley BS
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorRoger B. Sher PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorWayne N. Frankel PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorGregory A. Cox PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Search for more papers by this authorCorresponding Author
Kevin L. Seburn PhD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USASearch for more papers by this authorAbstract
The effective treatment or cure of motoneuron disease will require understanding the disease processes that precede irreversible cell loss. To study these early stages, and to evaluate potential treatments in relevant animal models, requires a sensitive functional assay. To this end, we sought to determine whether the gait pattern of SOD1 transgenic mice changed prior to overt symptoms. Using a simplified video-based approach we compared the treadmill gait of C57BL/6J and B6.SOD1 transgenic mice at 8 and 10 weeks of age. B6.SOD1 mice had significantly longer stride and stance times than controls by 8 weeks. Consistent with disease progression, hindpaw measures of B6.SOD1 mice showed larger changes than front paws. Differences between control and B6.SOD1 mice increased at 10 weeks, but only because repeat testing caused habituation in control mice to a greater extent than in B6.SOD1 mice. Together the results demonstrate that simplified gait analysis is sensitive to early processes of motor system disease in mice. Muscle Nerve, 2005
REFERENCES
- 1 Bittner RE, Anderson LV, Burkhardt E, Bashir R, Vafiadaki E, Ivanova S, et al. Dysferlin deletion in SJL mice (SJL-Dysf) defines a natural model for limb girdle muscular dystrophy 2B. Nat Genet 1999; 23: 141–142.
- 2 Buchner DM, Cress ME, Esselman PC, Margherita AJ, de Lateur BJ, Campbell AJ, et al. Factors associated with changes in gait speed in older adults. J Gerontol A Biol Sci Med Sci 1996; 51: M297–302.
- 3 Charteris J, Taves C. The process of habituation to treadmill walking: a kinematic analysis. Percept Mot Skills 1978; 47: 659–666.
- 4 Chiu AY, Zhai P, Dal Canto MC, Peters TM, Kwon YW, Prattis SM, et al. Age-dependent penetrance of disease in a transgenic mouse model of familial amyotrophic lateral sclerosis. Mol Cell Neurosci 1995; 6: 349–362.
- 5 Clarke KA, Still J. Gait analysis in the mouse. Physiol Behav 1999; 66: 723–729.
- 6 Clarke KA, Still J. Development and consistency of gait in the mouse. Physiol Behav 2001; 73: 159–164.
- 7 Costa AC, Walsh K, Davisson MT. Motor dysfunction in a mouse model for Down syndrome. Physiol Behav 1999; 68: 211–220.
- 8 Engsberg JR, Lauryssen C, Ross SA, Hollman JH, Walker D, Wippold FJ II. Spasticity, strength, and gait changes after surgery for cervical spondylotic myelopathy: a case report. Spine 2003; 28: E136–139.
- 9 Fiore C, Inman DM, Hirose S, Noble LJ, Igarashi T, Compagnone NA. Treatment with the neurosteroid dehydroepiandrosterone promotes recovery of motor behavior after moderate contusive spinal cord injury in the mouse. J Neurosci Res 2004; 75: 391–400.
- 10 Fischer LR, Culver DG, Tennant P, Davis AA, Wang M, Castellano-Sanchez A, et al. Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 2004; 185: 232–240.
- 11 Frankel WN. Mouse strain backgrounds: more than black and white. Neuron 1998; 20: 183.
- 12 Frey D, Schneider C, Xu L, Borg J, Spooren W, Caroni P. Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases. J Neurosci 2000; 20: 2534–2542.
- 13 Gronley JK, Perry J. Gait analysis techniques. Rancho Los Amigos Hospital gait laboratory. Phys Ther 1984; 64: 1831–1838.
- 14 Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 1994; 264: 1772–1775.
- 15 Hashimoto M, Rockenstein E, Masliah E. Transgenic models of alpha-synuclein pathology: past, present, and future. Ann NY Acad Sci 2003; 991: 171–188.
- 16 Jankowsky JL, Savonenko A, Schilling G, Wang J, Xu G, Borchelt DR. Transgenic mouse models of neurodegenerative disease: opportunities for therapeutic development. Curr Neurol Neurosci Rep 2002; 2: 457–464.
- 17 Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 2003; 301: 839–842.
- 18 Kennel PF, Finiels F, Revah F, Mallet J. Neuromuscular function impairment is not caused by motor neurone loss in FALS mice: an electromyographic study. Neuroreport 1996; 7: 1427–1431.
- 19 Kirkinezos IG, Hernandez D, Bradley WG, Moraes CT. Regular exercise is beneficial to a mouse model of amyotrophic lateral sclerosis. Ann Neurol 2003; 53: 804–807.
- 20 Klapdor K, Dulfer BG, Hammann A, Van der Staay FJ. A low-cost method to analyse footprint patterns. J Neurosci Methods 1997; 75: 49–54.
- 21 Leblond H, L'Esperance M, Orsal D, Rossignol S. Treadmill locomotion in the intact and spinal mouse. J Neurosci 2003; 23: 11411–11419.
- 22 Marsolais GS, Dvorak G, Conzemius MG. Effects of postoperative rehabilitation on limb function after cranial cruciate ligament repair in dogs. J Am Vet Med Assoc 2002; 220: 1325–1330.
- 23 Mohr KJ, Kvitne RS, Pink MM, Fideler B, Perry J. Electromyography of the quadriceps in patellofemoral pain with patellar subluxation. Clin Orthop 2003: 261–271.
- 24 Muybridge E. Human and animal locomotion. New York: Dover Publications; 1979.
- 25 Trieu VN, Uckun FM. Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke. Biochem Biophys Res Commun 1999; 258: 685–688.
- 26 Veldink JH, Bar PR, Joosten EA, Otten M, Wokke JH, van den Berg LH. Sexual differences in onset of disease and response to exercise in a transgenic model of ALS. Neuromuscul Disord 2003; 13: 737–743.
- 27 Vilensky JA, Patrick MC. Inter and intratrial variation in cat locomotor behavior. Physiol Behav 1984; 33: 733–743.
- 28 Wall JC, Charteris J. The process of habituation to treadmill walking at different velocities. Ergonomics 1980; 23: 425–435.
- 29 Wall JC, Charteris J. A kinematic study of long-term habituation to treadmill walking. Ergonomics 1981; 24: 531–542.