Molecular cause of the severe functional deficiency in osteoclasts by an arginine deletion in the basic domain of Mi transcription factor

Abstract

Severe osteopetrosis was observed in mi/mi mutant mice. However, the bone of VGA9/VGA9 mutant mice, in which Mi gene expression is undetectable, showed normal histology. No osteopetrosis was found in mi/+ mice, but was observed in VGA9/mi mice. Biochemical analysis revealed that the gene product encoded with the mi mutant allele (mi–Mi) has impared DNA binding activity and nuclear translocation ability. Furthermore, inhibitory effects of mi–Mi were shown not only on the DNA binding activity of wild-type Mi, but also on the nuclear translocation ability of Mi, PU.1 and cFOS. The present results suggest the presence of a target gene for Mi that is essential for the proliferation/differentiation of osteoclasts.