期刊文献+
共找到1篇文章
< 1 >
每页显示 20 50 100
A mutation in TBXT causes congenital vertebral malformations in humans and mice
1
作者 Shuxia Chen Yunping Lei +6 位作者 Yajun Yang Chennan Liu Lele Kuang Li Jin Richard HFinnell Xueyan Yang Hongyan Wang 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2024年第4期433-442,共10页
T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal development.Although it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs... T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal development.Although it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well established.Here,we report a family with 15 CVM patients distributed across 4 generations.All affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and phenotype.In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the wild-type.To determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM phenotype.Most heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral deformities.Overall,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM. 展开更多
关键词 Congenital vertebral malformation TBXT T gene Loss-of-function mutation
原文传递
上一页 1 下一页 到第
使用帮助 返回顶部