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, M. Palkóvits, Wolfgang H. Sommer, Christian R. Andres

Research output: Contribution to journalArticle

3 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

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Alleles
Population
Genes
Single Nucleotide Polymorphism
Nogo Receptor 1
Nogo Receptors
Amyotrophic lateral sclerosis 1
Motor Neuron Disease
Messenger RNA
Genetically Modified Animals
Brain
Motor Neurons
Transgenic Mice
Genotype
Gene Expression
Muscles
Polymerase Chain Reaction

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population. / Amy, Maïté; Staehlin, Oliver; René, Frédérique; Blasco, Hélène; Marouillat, Sylviane; Daoud, Hussein; Vourch, Patrick; Gordon, Paul H.; Camu, William; Corcia, Philippe; Loeffler, Jean Philippe; Palkóvits, M.; Sommer, Wolfgang H.; Andres, Christian R.

In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Vol. 16, No. 7-8, 27.11.2015, p. 490-496.

Research output: Contribution to journalArticle

Amy, M, Staehlin, O, René, F, Blasco, H, Marouillat, S, Daoud, H, Vourch, P, Gordon, PH, Camu, W, Corcia, P, Loeffler, JP, Palkóvits, M, Sommer, WH & Andres, CR 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, vol. 16, no. 7-8, pp. 490-496. https://doi.org/10.3109/21678421.2015.1051988
Amy, Maïté ; Staehlin, Oliver ; René, Frédérique ; Blasco, Hélène ; Marouillat, Sylviane ; Daoud, Hussein ; Vourch, Patrick ; Gordon, Paul H. ; Camu, William ; Corcia, Philippe ; Loeffler, Jean Philippe ; Palkóvits, M. ; Sommer, Wolfgang H. ; Andres, Christian R. / A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population. In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2015 ; Vol. 16, No. 7-8. pp. 490-496.
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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.",
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AU - Staehlin, Oliver

AU - René, Frédérique

AU - Blasco, Hélène

AU - Marouillat, Sylviane

AU - Daoud, Hussein

AU - Vourch, Patrick

AU - Gordon, Paul H.

AU - Camu, William

AU - Corcia, Philippe

AU - Loeffler, Jean Philippe

AU - Palkóvits, M.

AU - Sommer, Wolfgang H.

AU - Andres, Christian R.

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N2 - 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.

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