Meta-analysis of gene expression profiling in amyotrophic lateral sclerosis: A comparison between transgenic mouse models and human patients

Christiaan G. J. Saris, Ewout J. N. Groen, Johan A. F. Koekkoek, Jan H. Veldink, Leonard H. Van den Berg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The exact pathogenic cascade leading to motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is unknown. Gene expression profiles of ALS-affected spinal cord and motor neurons have been well established in mice and man. We provide a meta-analysis of the reported significant gene lists of gene expression studies in ALS, and compare results between mouse models and human post mortem tissue. In total, 12 articles met inclusion criteria. Twenty-nine genes were found to be differentially expressed at least twice in studies using human post mortem tissue, enriched for the functions 'immune response', 'apoptosis' and 'protein metabolism'. In mouse studies, 86 genes were reported at least two times and were enriched for 'immune response', 'lysosome', 'metal ion binding' and 'mitochondrion'. Next, all differentially expressed genes from the mouse studies were translated to human homologous genes. Seventy-four differentially expressed genes in mouse tissue were also found to be differentially expressed in human tissue. In conclusion, evidence was found for shared dysfunction in protein turnover in the ubiquitin-proteasome system. Differential expression of Cathepsin B and D, GFAP and SERPINA3 was repeatedly found to be significant in both the mouse model and ALS patients.

Original languageEnglish
Pages (from-to)177-189
Number of pages13
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume14
Issue number3
DOIs
Publication statusPublished - Apr 2013

Keywords / Materials (for Non-textual outputs)

  • RNA
  • transgenic animals
  • SOD1
  • ubiquintin
  • MOTOR-NEURON DISEASE
  • SPINAL-CORD
  • DIFFERENTIAL EXPRESSION
  • MUTANT SOD1
  • MICROARRAY ANALYSIS
  • FAMILIAL ALS
  • MURINE MODEL
  • ADULT-ONSET
  • COMPLEMENT
  • BIOMARKERS

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