{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328153/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"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=GSE328153"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A mouse model of Free Sialic Acid Storage Disorder: Hypomyelinating leukodystrophy and Purkinje cell degeneration","description":"Free sialic acid storage disorder (FSASD) is a rare, neurodegenerative lysosomal storage disease caused by biallelic variants in SLC17A5, which encodes the lysosomal sialic acid exporter sialin. Although clinical severity varies, all affected individuals exhibit progressive neurological decline and characteristic lysosomal and urinary accumulation of free sialic acid, and no FDA-approved therapies currently exist, with the molecular basis of central nervous system dysfunction remaining poorly defined. To model the most prevalent disease-associated allele, a Slc17a5R39C mouse carrying the pathogenic p.Arg39Cys variant was generated using CRISPR/Cpf1. Homozygous Slc17a5R39C/R39C mice recapitulate key features of FSASD, including biochemical accumulation of free sialic acid, progressive ataxia, tremors, seizures, and reduced lifespan. Neuropathological analyses demonstrate widespread central nervous system hypomyelination with relative preservation of peripheral myelination, while transcriptomic profiling reveals broad suppression of myelin-associated genes alongside a cerebellum-specific inflammatory signature. These changes are accompanied by marked astrogliosis, progressive Purkinje cell degeneration, and increased neurofilament proteins, including serum NfL. Collectively, the Slc17a5R39C/R39C model provides critical insight into disease pathogenesis, highlights region-specific neurodegenerative vulnerability, and establishes a robust preclinical platform for mechanistic and therapeutic studies.","dates":{"publication":"2026/04/30"},"accession":"GSE328153","cross_references":{"GSM":["GSM9673192","GSM9673181","GSM9673182","GSM9673171","GSM9673193","GSM9673194","GSM9673183","GSM9673172","GSM9673184","GSM9673173","GSM9673185","GSM9673174","GSM9673186","GSM9673175","GSM9673187","GSM9673176","GSM9673188","GSM9673177","GSM9673189","GSM9673178","GSM9673179","GSM9673190","GSM9673191","GSM9673180"],"GPL":["21103"],"GSE":["328153"],"taxon":["Mus musculus"]}}