《生命科学》 2018, 30(8): 855-861

LRP4与人类罕见遗传病

邵金辉，王志浩，刘　聪，吕赵劼，田　静*

(西北大学生命科学学院，西部资源生物与现代生物技术教育部重点实验室，西安 710069)

摘　要：摘　要：低密度脂蛋白受体相关蛋白4 (low-density lipoprotein receptor-related protein 4， LRP4) 在2010 年被报道确认为CLS 型并指综合征(Cenani-Lenz syndactyly syndrome) 的致病基因，相继有文献报道了LRP4的突变会造成17 型先天性肌无力症(myasthenic syndrome， congenital 17) 和二型硬化性骨病(sclerosteosis 2)。LRP4 参与调节经典WNT 信号通路和MAPK/JNK 信号通路，在神经肌肉接头中与MUSK/AGRIN 组成复
    合物，调节突触后转化。LRP4 参与肢端、神经肌肉接头、肾脏、乳腺和牙齿的发育形成，参与骨代谢进程。现将重点介绍LRP4 在人类中所引起的3 种单基因疾病和从遗传发育角度综述目前关于LRP4 的研究进展，对未来深入研究LRP4 在脊椎动物早期发育中的功能机制提供一定的参考。

LRP4 and human rare genetic diseases

SHAO Jin-Hui， WANG Zhi-Hao， LIU Cong， LYU Zhao-Jie， TIAN Jing*

(Key Laboratory of Resource Biology and Biotechnology in Western China， Ministry of Education， Northwest University， Xi’an 710069， China)

Abstract: Abstract: Low-density lipoprotein receptor-related protein 4 gene(LRP4)was identified as Cenani-Lenz syndactyly syndrome causative gene in 2010. Recent studies also found the mutations in LRP4 cause congenital myasthenic syndrome 17 and sclerosteosis 2. LRP4 is involved in regulating the canonical WNT signal pathway and the MAPK/JNK signal pathway; and in the neuromuscular junction， LRP4 binding with MUSK/AGRIN complex regulates postsynaptic transformation. LRP4 participates in the limbs， neuromuscular junction， kidneys， mammary glands and teeth development， as well as the bone metabolism process. Here we summarize three kinds of human rare genetic diseases caused by LRP4 and latest developmental and genetic studies of LRP4. The review will provide a reference
    for further studies on the functional mechanism of LRP4 in the early development of vertebrates.