mafB Deficient Mouse Results in Impaired Macrophage Differentiation.

MafB is one of the large Maf (musculoaponeurotic fibrosarcoma) proteins sharing a structurally similar basic region/leucine zipper DNA binding motif and a putative activation domain at the N-terminus. MafB is known to be expressed in the myelomonocytic lineages of hematopoietic cells. The recent in vitro experiments showed that the forced MafB expression induced monocytic differentiation of myeloblast progenitors, suggesting MafB could be the critical determinant in monocyte/macrophage differentiation. Nevertheless, the precise expression pattern and the physiological function of MafB in hematopoietic cells have never been analyzed in vivo setting. To address these issues, we have generated mafB locus GFP knock-in mouse. In E14.5 mafB GFP knock-in heterozygous embryos, GFP expression was specifically observed in F4/80 (differentiated macrophage marker) positive fetal liver cells. In homozygous mutant, expression of F4/80+ was significantly decreased in the neonatal liver, spleen and peripheral blood. Interestingly, the colony assay using E14.5 fetal liver cells revealed that the number of macrophage colony was significantly increased in homozygous mutant under the M-CSF supplemented condition, whereas the colony size was dramatically reduced, suggesting MafB deficiency prevent the terminal macrophage differentiation of fetal liver cells, then evoked the abnormal accumulation of premature progenitors. In the macrophages of homozygous mutant obtained by in vitro fetal liver differentiation, F4/80 expression and phagocytotic activity was dramatically suppressed compared to the wild type control. These observations strongly suggest that MafB is indispensable for the differentiation and the functional maturation of macrophages.