四个小说RUNX2突变包括剪接提供导致cleidocranial发育异常表型。
文章的细节
-
引用
复制到剪贴板 -
金黄建忠、南SH Kim HJ公园HS, Ryoo嗯,金SY,曹TJ,金正日SG, Bae SC,金正日,斯坦杰,van Wijnen AJ,崔斯坦GS、JB,客户至上
四个小说RUNX2突变包括剪接提供导致cleidocranial发育异常表型。
J细胞杂志。2006年4月,207(1):114 - 22所示。doi: 10.1002 / jcp.20552。
- PubMed ID
-
16270353 (在PubMed]
- 文摘
-
Cleidocranial发育不良(CCD)是一种常染色体显性遗传疾病引起的haploinsufficiency RUNX2的基因。在这项研究中,我们分析了由11个CCD直接测序RUNX2突变的病人。四个七突变的小说:两个无意义突变导致平移停在密码子50 (Q50X)和112 (E112X);无义突变将精氨酸甘氨酸密码子131 (R131G);和一个外显子1剪接提供突变(拼接供体GT /, IVS1 + 1 g >),外显子1-intron结导致删除QA RUNX2的第1外显子中包含的延伸。我们关注的功能分析IVS1 + 1 g >突变。这种突变的全长cDNA克隆(RUNX2Deltae1)和表达的中国仓鼠卵巢(CHO)和海拉细胞。功能分析执行RUNX2Deltae1对蛋白质稳定性、核本地化,DNA结合,transactivation下游RUNX2目标基因的活动。蛋白质的稳定性RUNX2Deltae1类似于野生型RUNX2由免疫印迹分析。RUNX2Deltae1的亚细胞定位,评估原位immunofluorescent染色,观察与部分保留在细胞核和细胞质。 This finding is in contrast to RUNX2 wild-type, which is detected exclusively in the nucleus. DNA binding activity was also compromised by the RUNX2Deltae1 in gel shift assay. Finally, RUNX2Deltae1 blocked transactivation of the osteocalcin gene determined by transient transfection assay. Our findings demonstrate for the first time that the CCD phenotype can be caused by a splice site mutation, which results in the deletion of N-terminus amino acids containing the QA stretch in RUNX2 that contains a previously unidentified second nuclear localization signal (NLS). We postulate that the QA sequence unique to RUNX2 contributes to a competent structure of RUNX2 that is required for nuclear localization, DNA binding, and transactivation function.