학술논문
A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population.
Document Type
Article
Author
Source
Subject
*NOGO receptors
*AMYOTROPHIC lateral sclerosis
*SINGLE nucleotide polymorphisms
*MOTOR neurons
*GENE expression
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Language
ISSN
2167-8421
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 thereticulon 4 receptorgeneRTN4Rwhich 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 theRTN4Rgene in 364 SALS French patients and 430 controls. We examined expression ofRTN4RmRNA by quantitative PCR in control post mortem human brain tissue. We determined the expression of NgR1 protein in spinal motor neurons from aSOD1G86R ALS mouse model. We observed significant associations between SALS andRTN4Ralleles. Messenger RNA expression fromRTN4Rin 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 functionalRTN4Rgene variant is associated with SALS. This variant may act in concert with other genetic variants or environmental influences. [ABSTRACT FROM AUTHOR]