A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population

Maïté Amy, Oliver Staehlin, Frédérique René, Hélène Blasco, Sylviane Marouillat, Hussein Daoud, Patrick Vourch, Paul H. Gordon, William Camu, Philippe Corcia, Jean Philippe Loeffler, Miklós Palkovits, Wolfgang H. Sommer, Christian R. Andres

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis is sporadic (SALS) in 90% of cases and has complex environmental and genetic influences. Nogo protein inhibits neurite outgrowth and is overexpressed in muscle in ALS. Our aims were to study the reticulon 4 receptor gene RTN4R which encodes Nogo 1 receptor (NgR1) in SALS, to test if the variants were associated with variable expression of the gene and whether NgR1 protein expression was modified in a transgenic mouse model of ALS. We genotyped three single nucleotide polymorphisms (SNPs; rs701421, rs701427, and rs1567871) of the RTN4R gene in 364 SALS French patients and 430 controls. We examined expression of RTN4R mRNA by quantitative PCR in control post mortem human brain tissue. We determined the expression of NgR1 protein in spinal motor neurons from a SOD1 G86R ALS mouse model. We observed significant associations between SALS and RTN4R alleles. Messenger RNA expression from RTN4R in human cortical brain tissue correlated significantly with the genotypes of rs701427. NgR1 protein expression was reduced in Nogo A positive motor neurons from diseased transgenic animals. In conclusion, these observations suggest that a functional RTN4R gene variant is associated with SALS. This variant may act in concert with other genetic variants or environmental influences.

Original languageEnglish
Pages (from-to)490-496
Number of pages7
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume16
Issue number7-8
DOIs
Publication statusPublished - Nov 27 2015

Keywords

  • Nogo-66 receptor
  • SNP
  • association study
  • gene expression
  • motor neurons
  • reticulon 4 receptor gene (RTN4R)
  • sporadic amyotrophic lateral sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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  • Cite this

    Amy, M., Staehlin, O., René, F., Blasco, H., Marouillat, S., Daoud, H., Vourch, P., Gordon, P. H., Camu, W., Corcia, P., Loeffler, J. P., Palkovits, M., Sommer, W. H., & Andres, C. R. (2015). A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 16(7-8), 490-496. https://doi.org/10.3109/21678421.2015.1051988