The mouse C9ORF72 ortholog is enriched in neurons known to degenerate in ALS and FTD

Nat Neurosci. 2013 Dec;16(12):1725-7. doi: 10.1038/nn.3566. Epub 2013 Nov 3.

Abstract

Using transgenic mice harboring a targeted LacZ insertion, we studied the expression pattern of the C9ORF72 mouse ortholog (3110043O21Rik). Unlike most genes that are mutated in amyotrophic lateral sclerosis (ALS), which are ubiquitously expressed, the C9ORF72 ortholog was most highly transcribed in the neuronal populations that are sensitive to degeneration in ALS and frontotemporal dementia. Thus, our results provide a potential explanation for the cell type specificity of neuronal degeneration caused by C9ORF72 mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Animals, Newborn
  • Brain / pathology*
  • C9orf72 Protein
  • Cells, Cultured
  • Embryo, Mammalian
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / pathology
  • Gene Expression Regulation / genetics*
  • Genotype
  • Guanine Nucleotide Exchange Factors / metabolism
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurons / pathology*
  • Nuclear Proteins / metabolism
  • Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcription Factors
  • Transfection

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • C9orf72 protein, mouse
  • CUX1 protein, human
  • Guanine Nucleotide Exchange Factors
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Proteins
  • Repressor Proteins
  • Transcription Factors
  • Acetylcholinesterase