Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson R T, Gao Y H, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T
Department of Medicine III, Osaka University Medical School, Suita, Japan.
Cell. 1997 May 30;89(5):755-64. doi: 10.1016/s0092-8674(00)80258-5.
A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is expressed restrictively in fetal development. To elucidate the function of Cbfa1, we generated mice with a mutated Cbfa1 locus. Mice with a homozygous mutation in Cbfa1 died just after birth without breathing. Examination of their skeletal systems showed a complete lack of ossification. Although immature osteoblasts, which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin, and a few immature osteoclasts appeared at the perichondrial region, neither vascular nor mesenchymal cell invasion was observed in the cartilage. Therefore, our data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.
一种属于 runt 结构域基因家族的转录因子 Cbfa1，在胎儿发育过程中受到限制表达。为了阐明 Cbfa1 的功能，我们构建了 Cbfa1 基因座发生突变的小鼠。Cbfa1 纯合突变的小鼠出生后即死亡，没有呼吸。对其骨骼系统的检查显示完全缺乏骨化。尽管在软骨膜区域出现了表达碱性磷酸酶较弱但不表达骨桥蛋白和骨钙素的未成熟成骨细胞以及一些未成熟破骨细胞，但在软骨中未观察到血管或间充质细胞侵入。因此，我们的数据表明，由于突变小鼠中成骨细胞的成熟停滞，膜内成骨和软骨内成骨均被完全阻断，并证明 Cbfa1 在骨生成中起重要作用。
