{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE231nnn/GSE231531/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231531"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Up-regulation of cholesterol synthesis pathways and neurodegeneration in a knock-in Sod1 mutant mouse model of ALS.","description":"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.","dates":{"publication":"2026/05/01"},"accession":"GSE231531","cross_references":{"GSM":["GSM7287780","GSM7287781","GSM7287782","GSM7287783","GSM7287784","GSM7287785","GSM7287786","GSM7287787","GSM7287788","GSM7287789","GSM7287800","GSM7287801","GSM7287802","GSM7287803","GSM7287804","GSM7287805","GSM7287806","GSM7287807","GSM7287808","GSM7287809","GSM7287790","GSM7287791","GSM7287792","GSM7287770","GSM7287793","GSM7287771","GSM7287772","GSM7287794","GSM7287795","GSM7287773","GSM7287796","GSM7287774","GSM7287775","GSM7287797","GSM7287798","GSM7287776","GSM7287810","GSM7287799","GSM7287777","GSM7287778","GSM7287811","GSM7287812","GSM7287779","GSM7287813"],"GPL":["24247"],"GSE":["231531"],"taxon":["Mus musculus"]}}