GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347488/primaryOK200OtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347488GEOGSEfalseA Hyper-IgM2 AID Mutation Limits IgH Break Formation but Preserves Affinity MaturationActivation-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.2026/09/20GSE347488GSM10054112GSM10054111GSM10054110GSM10054116GSM10054115GSM10054114GSM10054113GSM10054109GSM1005410824247347488Mus musculus