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

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 hPFN1(G118V) mice and their wildtype transgenic hPFN1(WT) controls at a pre-symptomatic stage and at the end-stage of disease. Analyses revealed that end-stage hPFN1(G118V) mice had 890 differentially expressed genes (747 up-regulated, 143 down-regulated) when compared to pre-symptomatic hPFN1(G118V) mice, and they had 836 differentially expressed genes (742 up-regulated, 94 down-regulated) when compared to age-matched hPFN1(WT) controls. Pre-symptomatic hPFN1(G118V) mice were not significantly different from age-matched hPFN1(WT) controls. Ingenuity Pathway Analysis identified inflammatory pathways significantly activated in end-stage hPFN1(G118V) 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 mechanisms of neurodegeneration that could potentially serve as therapeutic targets for ALS.