利用转基因小鼠探讨il-17rc基因突变在青少年特发性脊柱侧弯发生与发展中的作用

青少年特发性侧弯（AIS）是一种常见的脊柱三维畸形，但具体病因仍不明确；AIS患者常伴有一种全身性的骨质疏松，但病因亦不明确。本课题前期研究发现il-17rc基因rs708567位点突变与AIS的发生、发展及骨密度显著相关。该突变为外显子编码框内Ser向Leu的错义突变，可导致IL-17RC蛋白结构异常；而IL-17RC蛋白可通过调节RANKL/RANK信号因子的表达，实现对骨组织代谢的调节。基于以上发现，课题组推测il-17rc基因突变可能是导致AIS发生、发展及骨质疏松的病因之一。因此，本次课题拟利用mut-il-17rc-rs708567单碱基突变小鼠构建一种具有AIS遗传特征的AIS动物模型，以明确mut-il-17rc-rs708567突变是否为导致AIS发生、发展或者AIS患者骨质疏松症的病因之一。本课题的顺利开展对揭示AIS的遗传学病因具有重要意义。

Adolescent idiopathic scoliosis (AIS) is a common three-dimensional spinal deformity; in addition, it has been documented that AIS patients often accompanied by a systemic osteoporosis. However, the specific cause of AIS and the systemic osteoporosis still remains unclear. Preliminary findings of the present study have shown that rs708567 locus mutation in IL-17RC gene was significantly correlated with the occurrence and development of AIS and the BMD of AIS patients. rs708567 locus located in the IL-17RC gene exon region, and the point mutation can lead to a missense mutation from Leu to Ser, resulting in abnormal IL-17RC protein structure. IL-17RC protein is an important part of the IL-17/IL-17RC signal path which can activate the RANKL/RANK signal path and realize the bone tissue metabolism regulation. Based on the above study background, the purpose of this study is to confirm the role of rs708567 locus mutation in IL-17RC gene in the cause of AIS and the osteoporosis in AIS patients by using an IL-17RC gene rs708567 locus mutation mouse model.