MRI detects early hindlimb muscle atrophy in Gly93Ala superoxide dismutase-1 (G93A SOD1) transgenic mice, an animal model of familial amyotrophic lateral sclerosis.
MRI has been used to measure hindlimb muscle volume in female and male transgenic mice overexpressing the Gly93Ala (G93A) mutant human superoxide dismutase 1 (SOD1), a widely used model of familial amyotrophic lateral sclerosis (FALS), over the first 4 months of life. Significant decreases in the hindlimb muscle volume of the female G93A SOD1 mice were evident from 11 weeks of age, before other overt pathology appeared. By 15 weeks volume had decreased by 37% compared with 7 weeks, from 0.84+/-0.04 cm(3) (mean+/-standard deviation, n = 6) to 0.54+/-0.07 cm(3), (p < 0.05), despite an increase in body weight of ca. 12% (from 16.2 +/- 1.4 to 18.1 +/- 0.7 g). Female wild-type volume increased by ca. 30% whilst the body weight increased by 15%. Muscle wasteage was less (0.82+/-0.1 to 0.65+/-0.02 cm(3), p < 0.05, n = 6) in male G93A SOD1 mice between 8 and 16 weeks of age, against a body weight increase trend from 20.7 +/- 0.4 to 21.6 +/- 0.5 g, (p > 0.05). Wild-type male muscle volume did not change significantly over this period, with an increase in body weight of 20%. Longitudinal MRI hindlimb muscle volume measurements may provide a straightforward, rapid, non-invasive and sensitive, way of monitoring outcome of experimental ALS treatments.
Brooks
Keith J
KJ
GlaxoSmithKline, The Frythe, Welwyn, Herts AL6 9AR, UK.
Hill
Mark D W
MD
Hockings
Paul D
PD
Reid
David G
DG
D000375:Aging / Q000235:genetics / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006614:Hindlimb; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism; D009133:Muscular Atrophy / Q000175:diagnosis* / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1