GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE231nnn/GSE231531/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231531GEOGSEfalseUp-regulation of cholesterol synthesis pathways and neurodegeneration in a knock-in Sod1 mutant mouse model of ALS.Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder affecting brain and spinal cord motor neurons. Mutations in the copper/zinc superoxide dismutase gene (SOD1) are associated with ~20% of inherited and 1-2% of sporadic ALS cases. Much has been learned from mice expressing transgenic copies of mutant SOD1, which typically involve high-level transgene expression, thereby differing from ALS patients expressing one mutant gene copy. We created a knock-in point mutation in the endogenous mouse Sod1 gene leading to mutant SOD1G85R protein expression, a human ALS-causing mutation, to generate a model that more closely represents patient gene expression. Heterozygous Sod1G85R mutant mice resemble wild type, whereas homozygous mutants have reduced body weight and lifespan, a mild neurodegenerative phenotype, and express very low mutant SOD1 protein levels with no detectable SOD1 activity. Homozygous mutants exhibit partial neuromuscular junction denervation at 3-4 months of age. Spinal cord motor neuron transcriptome analyses of homozygous Sod1G85R mice revealed up-regulation of cholesterol synthesis pathway genes compared to wild type. Transcriptome and phenotypic features of these mice are similar to Sod1 knock-out mice, suggesting the Sod1G85R phenotype is largely driven by loss of SOD1 function. By contrast, cholesterol synthesis genes are down-regulated in severely affected human TgSOD1G93A transgenic mice at 4 months. Our analyses implicate dysregulation of cholesterol or related lipid pathway genes in ALS pathogenesis. The Sod1G85R knock-in mouse is a useful ALS model to examine the importance of SOD1 activity in control of cholesterol homeostasis and motor neuron survival.2026/05/01GSE231531GSM7287780GSM7287781GSM7287782GSM7287783GSM7287784GSM7287785GSM7287786GSM7287787GSM7287788GSM7287789GSM7287800GSM7287801GSM7287802GSM7287803GSM7287804GSM7287805GSM7287806GSM7287807GSM7287808GSM7287809GSM7287790GSM7287791GSM7287792GSM7287770GSM7287793GSM7287771GSM7287772GSM7287794GSM7287795GSM7287773GSM7287796GSM7287774GSM7287775GSM7287797GSM7287798GSM7287776GSM7287810GSM7287799GSM7287777GSM7287778GSM7287811GSM7287812GSM7287779GSM728781324247231531Mus musculus