Ablation of ZBTB24 in hematopoietic cells in mice results in antibody deficiency that mimics ICF syndrome

ICF syndrome, a rare autosomal recessive disorder characterized by immunodeficiency, centromeric instability and facial anomalies, is caused by mutations in DNMT3B, ZBTB24, CDCA7 or HELLS. In this study we show that mice deficient for Zbtb24 in the hematopoietic lineage exhibit a phenotype that recapitulates major clinical features of ICF patients, including hypogammaglobulinemia. RNA-Seq analysis of splenic follicular B cells and marginal zone B cells identifies dozens of genes that show differential expression in the absence of Zbtb24. These include Cdca7, Taf6, Cdc40, Ostc, Crisp3 and Il5ra. Overall design: Follicular (FO) B cells and marginal zone (MZ) B cells mRNA profiles of 8-12 weeks old VAVcre (Control) and VAVcre-Zbtb24 (CKO) mice