Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; Department of Orthopedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
J Biol Chem. 2011 Dec 23;286(51):43925-43932. doi: 10.1074/jbc.M111.264192. Epub 2011 Nov 2.
RB1-inducible coiled-coil 1 (RB1CC1) functions in various processes, such as cell growth, differentiation, senescence, apoptosis, and autophagy. The conditional transgenic mice with cartilage-specific RB1CC1 excess that were used in the present study were made for the first time by the Cre-loxP system. Cartilage-specific RB1CC1 excess caused dwarfism in mice without causing obvious abnormalities in endochondral ossification and subsequent skeletal development from embryo to adult. In vitro and in vivo analysis revealed that the dwarf phenotype in cartilaginous RB1CC1 excess was induced by reductions in the total amount of cartilage and the number of cartilaginous cells, following suppressions of type II collagen synthesis and Erk1/2 signals. In addition, we have demonstrated that two kinds of SNPs (T-547C and C-468T) in the human RB1CC1 promoter have significant influence on the self-transcriptional level. Accordingly, human genotypic variants of RB1CC1 that either stimulate or inhibit RB1CC1 transcription in vivo may cause body size variations.
RB1 诱导卷曲螺旋蛋白 1（RB1CC1）在多种过程中发挥作用，如细胞生长、分化、衰老、凋亡和自噬。本研究中使用的软骨特异性 RB1CC1 过表达条件性转基因小鼠是首次通过 Cre-loxP 系统构建的。软骨特异性 RB1CC1 过表达导致小鼠出现侏儒症，而不会引起胚胎到成年期间软骨内骨化和随后的骨骼发育的明显异常。体外和体内分析表明，软骨细胞 RB1CC1 过表达的侏儒表型是由于 II 型胶原合成和 Erk1/2 信号的抑制导致软骨总量和软骨细胞数量减少而引起的。此外，我们已经证明了人类 RB1CC1 启动子中的两种 SNP（T-547C 和 C-468T）对自我转录水平有显著影响。因此，体内刺激或抑制 RB1CC1 转录的人类 RB1CC1 基因型变异可能导致体型变化。
