EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway
文献类型：期刊论文
| 作者 | Wu, J; Yang, Y; He, Y; Li, Q; Wang, X; Sun, CJ; Wang, LS; An, Y; Luo, FH |
| 刊名 | HUMAN GENOMICS
 |
| 出版日期 | 2019 |
| 卷号 | 13期号:1页码:- |
| 关键词 | TREACHER-COLLINS-SYNDROME MANDIBULOFACIAL DYSOSTOSIS ESOPHAGEAL ATRESIA MENTAL-RETARDATION HAPLOINSUFFICIENCY PHENOTYPE MUTATION GROWTH PATHOGENESIS EXPRESSION |
| ISSN号 | 1473-9542 |
| DOI | 10.1186/s40246-019-0238-y |
| 文献子类 | 期刊论文 |
| 英文摘要 | Background: Mandibulofacial dysostosis with microcephaly (MFDM) is characteristic of multiple skeletal anomalies comprising craniofacial anomalies/dysplasia, microcephaly, dysplastic ears, choanal atresia, and short stature. Heterozygous loss of function variants of EFTUD2 was previously reported in MFDM; however, the mechanism underlying EFTUD2-associated skeletal dysplasia remains unclear. Results: We identified a novel frameshift variant of EFTUD2 (c.1030_1031delTG, p.Trp344fs*2) in an MFDM Chinese patient with craniofacial dysmorphism including ear canal structures and microcephaly, mild intellectual disability, and developmental delay. We generated a zebrafish model of eftud2 deficiency, and a consistent phenotype consisting of mandibular bone dysplasia and otolith loss was observed. We also showed that EFTUD2 deficiency significantly inhibited proliferation, differentiation, and maturation in human calvarial osteoblast (HCO) and human articular chondrocyte (HC-a) cells. RNA-Seq analysis uncovered activated TP53 signaling with increased phosphorylation of the TP53 protein and upregulation of five TP53 downstream target genes (FAS, STEAP3, CASP3, P21, and SESN1) both in HCO and in eftud2-/- zebrafish. Additionally, inhibition of p53 by morpholino significantly reduced the mortality of eftud2-/- larvae. Conclusions: Our results confirm a novel de novo variant of the EFTUD2 gene and suggest that EFTUD2 may participate in the maturation and differentiation of osteoblasts and chondrocytes, possibly via activation of the TP53 signaling pathway. Thus, mutations in this gene may lead to skeletal anomalies in vertebrates. |
| 语种 | 英语 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/32041]  |
| 专题 | 上海应用物理研究所_中科院上海应用物理研究所2011-2017年 |
| 作者单位 | 1.Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China; 2.Fudan Univ, Human Phenome Inst, 825 Zhangheng Rd, Shanghai 201203, Peoples R China 3.Fudan Univ, Dept Pediat Endocrinol & Inherited Metab Dis, Childrens Hosp, Shanghai 201102, Peoples R China; 4.Fudan Univ, Inst Pediat, Childrens Hosp, Shanghai 201102, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai Synchrotron Radiat Facil, 239 Zhangheng Rd, Shanghai 201204, Peoples R China; 6.Fudan Univ, Translat Med Ctr Dev & Dis, Shanghai Key Lab Birth Defect, Inst Pediat,Childrens Hosp, Shanghai 201102, Peoples R China; 7.Fudan Univ, Sch Basic Med Sci, Key Lab Metab & Mol Med, Minist Educ, Shanghai 200032, Peoples R China; 8.Fudan Univ, Minhang Hosp, Inst Fudan Minhang Acad Hlth Syst, 170 Xinsong Rd, Shanghai 201199, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wu, J,Yang, Y,He, Y,et al. EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway[J]. HUMAN GENOMICS,2019,13(1):-. |
| APA | Wu, J.,Yang, Y.,He, Y.,Li, Q.,Wang, X.,...&Luo, FH.(2019).EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway.HUMAN GENOMICS,13(1),-. |
| MLA | Wu, J,et al."EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway".HUMAN GENOMICS 13.1(2019):-. |
入库方式： OAI收割
来源：上海应用物理研究所
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