RNA-Seq Analysis of Spinal Cord Tissues from hPFN1G118V Transgenic Mouse Model of ALS at Pre-symptomatic and End-Stages of Disease

Scientific Reports
Caroline BarhamMahmoud Kiaei

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to the loss of motor neurons. The molecular mechanisms of motor neuron degeneration are largely unknown and there are currently no effective therapies to treat this disease. In this work, we report whole transcriptome profiling of spinal cords of mutant transgenic hPFN1G118V mice and their wildtype transgenic hPFN1WT controls at a pre-symptomatic stage and at the end-stage of disease. Analyses revealed that end-stage hPFN1G118V mice had 890 differentially expressed genes (747 up-regulated, 143 down-regulated) when compared to pre-symptomatic hPFN1G118V mice, and they had 836 differentially expressed genes (742 up-regulated, 94 down-regulated) when compared to age-matched hPFN1WT controls. Pre-symptomatic hPFN1G118V mice were not significantly different from age-matched hPFN1WT controls. Ingenuity Pathway Analysis identified inflammatory pathways significantly activated in end-stage hPFN1G118V samples, suggesting an excess of glial activation at end-stage disease, possibly due to an increase in glial composition within the spinal cord during disease progression. In conclusion, our RNA-Seq data identified molecules and pathways involved in the mec...Continue Reading

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Methods Mentioned

BETA
RNA-Seq
transgenic
PCA
PCR

Software Mentioned

R
TopHat
sva
IPA
Bioconductor
Cufflinks
Ingenuity Pathway Analysis software ( IPA
Trimmomatic
limma
FastQC

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