Molecular cause of the severe functional deficiency in osteoclasts by an arginine deletion in the basic domain of Mi transcription factor.
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 impaired 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.
Nomura
S
S
Department of Pathology, Osaka University Medical School, Suita, Japan.
Sakuma
T
T
Higashibata
Y
Y
Oboki
K
K
Sato
M
M
D021581:Active Transport, Cell Nucleus; D000483:Alleles; D000818:Animals; D001120:Arginine / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018257:Helix-Loop-Helix Motifs; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D051739:Microphthalmia-Associated Transcription Factor; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D010022:Osteopetrosis / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014157:Transcription Factors; D001120:Arginine