A missense mutation in AIOLOS causes B cell deficiency by interfering with IKAROS

A missense mutation (G158R) in Ikzf3 gene resulted in defective generation of B cells in mice. Pre-B cells were profoundly decreased in homozygous mutant mice. Heterozygous mutant mice showed milder B cell developmental defects, and decreased B cells in the secondary lymphoid organs were observed. Ikzf3 encodes Aiolos, which makes heterodimer with Ikaros. Our findings indicate that the loss-of-function mutation in Aiolos hinders B cell development by interfering Ikaros' function via formation of heterodimers. Sample 1-18: mRNA profiles of pre-pro B cells and pre-B cells in wild-type, heterozygous and homozygous Ikzf3 G158R mutant mice. Sample 19-30: Genome-wide bindings of Ikaros and Aiolos in pre-B cells and thymocytes of wild-type and homozygous Ikzf3 G158R mutant mice.