BMPR-IB gene disruption causes severe limb deformities in pigs

作     者：Qiang Yang Chuan-Min Qiao Wei-Wei Liu Hao-Yun Jiang Qi-Qi Jing Ya-Ya Liao Jun Ren Yu-Yun Xing Qiang Yang;Chuan-Min Qiao;Wei-Wei Liu;Hao-Yun Jiang;Qi-Qi Jing;Ya-Ya Liao;Jun Ren;Yu-Yun Xing

作者机构：State Key Laboratory of Pig Genetic Improvement and Production TechnologyJiangxi Agricultural UniversityNanchangJiangxi 330045China 

出 版 物：《Zoological Research》 (动物学研究（英文）)

年 卷 期：2022年第43卷第3期

页      面：391-403页

核心收录：

学科分类：0905[农学-畜牧学] 09[农学] 090501[农学-动物遗传育种与繁殖] 

基　　金：supported by the National Natural Science Foundation of China(31560304) National Key Research Programs of China(2016ZX08006-003) 

主　　题：BMPR-IB A746G Pigs Limb deformities 

摘      要：In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR-IB-/746G)via CRISPR/Cas9 *** chain reaction(PCR)and sequencing revealed complex genomic rearrangements in the target *** BMPR-IBdisrupted piglets showed an inability to stand and walk *** BMPR-IB^(-/-)and BMPR-IB-/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms(ulna,radius)and disordered carpal,metacarpal,and phalangeal bones in the *** piglets displayed more severe deformities in the hindlimbs by visual inspection,including fibular hemimelia,enlarged tarsal bone,and disordered toe joint *** deformities were more profound in BMPR-IB^(-/-)piglets than in the BMPR-IB-/746G *** analysis identified 139 differentially expressed proteins(DEPs)in the hindlimb fibula of BMPR-IB-/746G piglets compared to the wild-type(WT)*** DEPs are involved in skeletal or embryonic development and/or the TGF-βpathway and tumor *** Ontology(GO)and protein domain enrichment analysis suggested alterations in these *** the top 50 DEPs,a large proportion,e.g.,C1QA,MYO1H,SRSF1,P3H1,GJA1,TCOF1,RBM10,SPP2,MMP13,and PHAX,were significantly associated with skeletal *** study provides novel findings on the role of BMPR-IB in mammalian limb development.