{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338462/"]},"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=GSE338462"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"mTOR Signaling is a Key Modifier and Therapeutic Target in a Mouse Model of X-linked Alport Syndrome.","description":"X-linked Alport syndrome (XLAS) is a hereditary kidney disease with substantial phenotypic variability despite well-defined causal mutations in type IV collagen. To identify modifier pathways influencing disease severity, we previously generated and analyzed a population of ~200 genetically diverse mice with XLAS and identified two candidate genes associated with albuminuria (Dgke and Pik3r1) both involved in the PI3K-AKT-mTOR pathway. To investigate the involvement of the PI3K-AKT-mTOR pathway in XLAS, we inhibited mTOR with rapamycin and found that treatment extended time to renal failure by 44%, whereas partial mTORC2 reduction via Rictor haploinsufficiency did not alter disease. A multi-drug intervention showed that rapamycin, meclizine, and fisetin significantly reduced albumin-to-creatinine ratio (ACR) without improving glomerular filtration rate (GFR), indicating protection from kidney injury rather than restoration of filtration. Together, these findings highlight mTORC1 signaling as a key modifier of XLAS.","dates":{"publication":"2026/07/13"},"accession":"GSE338462","cross_references":{"GSM":["GSM9874799","GSM9874800","GSM9874797","GSM9874798","GSM9874803","GSM9874804","GSM9874801","GSM9874802","GSM9874795","GSM9874796","GSM9874793","GSM9874794"],"GPL":["34290"],"GSE":["338462"],"taxon":["Mus musculus"]}}