{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288803/"]},"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=GSE288803"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Proteasome inhibition alleviates proteinuria in Lmx1b knock-in mice with dysfunctional LIM domains","description":"LMX1B codes for a transcription factor of the LIM-homeodomain family, mutations in this gene cause the autosomal-dominant hereditary disease nail-patella syndrome. We have generated two knock-in mouse lines which carry missense mutations in the LIM domains of LMX1B and thus mimic the situation in patients. Surprisingly, both mouse lines only developed a phenotype in the recessive state. This is due to the misfolding of the respective LIM domains, in which a zinc-chelating amino acid was exchanged by an alternative amino acid, and the subsequent ubiquitin-dependent proteasomal degradation of mutant LMX1B. The proteasomal inhibitors bortezomib and MG132 stabilized the mutant proteins in vitro. A therapeutic study demonstrated that bortezomib markedly reduced podocyte damage and alleviated proteinuria in adult mice with a floxed and a knock-in Lmx1b allele. RNA sequencing of isolated podocytes from those mice revealed a number of genes which were up- or down-regulated in both knock-in mouse lines but also led to the identification to genes whose regulation specifically depended on the LIM-B domain. Our data provide proof of principle for a therapeutic strategy in patients with nail-patella syndrome suffering from missense mutations in the LIM domains of LMX1B","dates":{"publication":"2026/04/27"},"accession":"GSE288803","cross_references":{"GSM":["GSM8775817","GSM8775818","GSM8775784","GSM8775785","GSM8775786","GSM8775787","GSM8775788","GSM8775789","GSM8775800","GSM8775801","GSM8775802","GSM8775803","GSM8775804","GSM8775805","GSM8775806","GSM8775807","GSM8775808","GSM8775809","GSM8775790","GSM8775791","GSM8775792","GSM8775793","GSM8775794","GSM8775795","GSM8775796","GSM8775797","GSM8775798","GSM8775810","GSM8775799","GSM8775811","GSM8775812","GSM8775813","GSM8775814","GSM8775815","GSM8775816"],"GPL":["30172"],"GSE":["288803"],"taxon":["Mus musculus"]}}