Differential expression and alternative splicing of genes in lumbar spinal cord of an amyotrophic lateral sclerosis mouse model

Brain Res. 2010 Jun 22:1340:52-69. doi: 10.1016/j.brainres.2010.03.075. Epub 2010 Mar 31.

Abstract

Amyotrophic lateral sclerosis (ALS) is one of the most common adult-onset neurodegenerative diseases, with progressive paralysis and muscle atrophy. The exact pathogenic mechanism remains unknown, but recent evidence suggests that differential gene expression and gene splicing may play a significant role. We used Affymetrix GeneChip Mouse Exon 1.0 ST Array to investigate the expression profiling of lumbar spinal cord samples from SOD1-G93A transgenic mice, the widely used animal model of ALS. The de-regulated genes analyzed either from the expression level or from the alternative splicing level both showed overlapping GO categories and pathway mapping. Our findings indicate that cell adhesion, immune-inflammation response and lipid metabolism all play important roles in the onset of ALS. Detailed analysis by RT-PCR of key genes confirmed the experimental results of microarrays. These results suggest a multi-factor mechanism in ALS development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Cell Adhesion / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Humans
  • Lipid Metabolism / genetics
  • Lumbar Vertebrae
  • Metabolic Networks and Pathways / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Protein Isoforms / genetics
  • Signal Transduction / genetics
  • Spinal Cord / metabolism*
  • Spinal Cord / physiopathology

Substances

  • Nerve Tissue Proteins
  • Protein Isoforms