{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347488/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347488"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A Hyper-IgM2 AID Mutation Limits IgH Break Formation but Preserves Affinity Maturation","description":"Activation-induced cytidine deaminase (AID) drives antibody diversification through class switch recombination (CSR) and somatic hypermutation (SHM). Humans with an AID mutation deleting the last nine amino acids (AIDR190X) develop hyper-IgM syndrome with defective CSR but variable SHM, suggesting that the C-terminus plays a marked role in CSR. To model this putative separation-of-function mutation, we generated an AicdaR190X knock-in mouse. These mice show a severe CSR defect and a moderately reduced but ongoing SHM. Mechanistically, the severe CSR defect correlates with defective recombination of double-strand breaks in immunoglobulin switch regions. Strikingly, fusion of AIDR190X to a catalytically inactive AID restores CSR, indicating that the C-terminus mediates a non-catalytic function for recombination. This first mouse model of the human R190X mutation demonstrates that the AID C-terminus is indispensable for CSR and also contributes to efficient SHM, providing new insight into the mechanistic basis of hyper-IgM immunodeficiency.","dates":{"publication":"2026/09/20"},"accession":"GSE347488","cross_references":{"GSM":["GSM10054112","GSM10054111","GSM10054110","GSM10054116","GSM10054115","GSM10054114","GSM10054113","GSM10054109","GSM10054108"],"GPL":["24247"],"GSE":["347488"],"taxon":["Mus musculus"]}}