Loss of Bicra/Gltscr1 leads to a defect in fetal liver macrophages responsible for erythrocyte maturation in mice.

GLTSCR1, a protein encoded by the Bicra gene, is a defining subunit of the SWI/SNF (also called mammalian BAF) chromatin remodeling subcomplex called GBAF/ncBAF. To determine the role of GLTSCR1 during mouse development, we generated a Bicra germline knockout mouse using CRISPR/Cas9. Mice with homozygous loss of Bicra were born at Mendelian ratios but were small, pale and died within 24 hours after birth. Histology indicated blood-related defects including defective erythroblastic islands and irregularly sized red blood cells. Gene expression profiling of fetal livers pinpointed a defect in liver resident macrophages involved in the last stage of erythrocyte maturation, resulting in accumulation of nucleated erythrocytes in Bicra-/- pups. Together, these results demonstrate that Bicra is critical for fetal liver macrophage function during development.