title: Gene expression profile of SOD1-G93A mouse spinal cord, blood and muscle.
abstract: The exact pathway leading to neuron death and muscle atrophy in amyotrophic lateral sclerosis (ALS) has not yet been elucidated. Gene expression profile of spinal cord, blood and muscle could provide signalling pathways and systemic alterations useful for future biomarker development. In our study we compared whole genome expression profiles of lumbar spinal cord with peripheral blood and tibialis anterior muscle in 16 mutant SOD1-G93A mice and 15 wild-type littermates. In SOD1-G93A mice, 11 genes were significantly differentially expressed in spinal cord, and 16 genes in blood, while much larger transcriptional changes were noted in muscle (1745 genes significant; six overlapping with spinal cord (0.3%)) probably due to muscle atrophy. Overlap with spinal cord was enriched for significant genes in blood (six of 16 overlapping with spinal cord (37.5%)). Three genes were significantly down-regulated in all three tissues, and were closely related to mitochondrial function. Furthermore, clustering the significant genes in spinal cord and in blood, but not in muscle, could identify the SOD1-G93A mice. We conclude that blood gene expression profile overlapped with profile of spinal cord, allowing differentiation of SOD1-G93A mice from wild-type littermates. Blood gene expression profiling may be a promising biomarker for ALS patients.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Christiaan G J
authors.initials: CG
authors.lastname: Saris
authors.forename: Ewout J N
authors.initials: EJ
authors.lastname: Groen
authors.forename: Paul W J
authors.initials: PW
authors.lastname: van Vught
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.forename: Hylke M
authors.initials: HM
authors.lastname: Blauw
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000367:Age Factors; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology*; D013116:Spinal Cord / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000097:blood* / Q000235:genetics* / Q000378:metabolism
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase