RNA-Seq Analysis of Spinal Cord Tissues from hPFN1G118V Transgenic Mouse Model of ALS at Presymptomatic 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. Cases of familial ALS have been linked to mutations in the profilin1 gene (PFN1) and here we utilize the in vivo mouse model of PFN1-related motor neuron disease, hPFN1G118V. We conducted whole transcriptome profiling of spinal cords of mutant transgenic hPFN1G118V mice and their wildtype transgenic hPFN1WT controls at 50 days, a presymptomatic stage and the earliest known time point at which aggregation of PFN1G118V occurs, and at end stage of disease, beginning around 180 days. The overall transcriptome profiles of spinal cord were highly similar while end stage hPFN1G118V mice had gene expression that clustered away from hPFN1WT and presymptomatic hPFN1G118V mice. Differential expression analysis revealed that end stage hPFN1G118V mice had 890 differentially expressed genes (747 up and 143 down) when compared to pre-symptomatic hPFN1G118V mice, and they had 836 differentially expressed genes (742 up and 94 down) when compared to their age-matched hPFN1WT controls. 50 day old hPFN1G118V mice were not significantly different from their age matched hPFN1WT controls. This is the first study that has utilized next generation RNA-sequencing to measure gene expression in pre-symptomatic and end-stage hPFN1G118V mice, and may lead to identification of molecular features that could become therapeutic targets for ALS. RNA-sequencing of spinal cords of transgenic hPFN1G118V mice and transgenic hPFN1WT mice at presymptomatic and end stage of disease