Genetic biomarkers for ALS disease in transgenic SOD1(G93A) mice

PLoS One. 2012;7(3):e32632. doi: 10.1371/journal.pone.0032632. Epub 2012 Mar 7.

Abstract

The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1(G93A) mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1(G93A) mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1(G93A) mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Animals
  • Biopsy
  • Denervation
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Markers
  • Humans
  • Longevity / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Mutant Proteins / genetics*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1
  • Transcription, Genetic

Substances

  • Genetic Markers
  • Mutant Proteins
  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1