Volume 43 Issue 3
May  2022
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Qiang Yang, Chuan-Min Qiao, Wei-Wei Liu, Hao-Yun Jiang, Qi-Qi Jing, Ya-Ya Liao, Jun Ren, Yu-Yun Xing. BMPR-IB gene disruption causes severe limb deformities in pigs. Zoological Research, 2022, 43(3): 391-403. doi: 10.24272/j.issn.2095-8137.2021.291
Citation: Qiang Yang, Chuan-Min Qiao, Wei-Wei Liu, Hao-Yun Jiang, Qi-Qi Jing, Ya-Ya Liao, Jun Ren, Yu-Yun Xing. BMPR-IB gene disruption causes severe limb deformities in pigs. Zoological Research, 2022, 43(3): 391-403. doi: 10.24272/j.issn.2095-8137.2021.291

BMPR-IB gene disruption causes severe limb deformities in pigs

doi: 10.24272/j.issn.2095-8137.2021.291
#Authors contributed equally to this work
Funds:  This work was supported by the National Natural Science Foundation of China (31560304) and National Key Research Programs of China (2016ZX08006-003)
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  • Corresponding author: E-mail: xingyuyun9@hotmail.com
  • Received Date: 2022-01-17
  • Accepted Date: 2022-03-31
  • Published Online: 2022-03-31
  • Publish Date: 2022-05-18
  • 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 editing. Polymerase chain reaction (PCR) and sequencing revealed complex genomic rearrangements in the target region. All BMPR-IB-disrupted piglets showed an inability to stand and walk normally. Both 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 forelimbs. The piglets displayed more severe deformities in the hindlimbs by visual inspection, including fibular hemimelia, enlarged tarsal bone, and disordered toe joint bones. Limb deformities were more profound in BMPR-IB-/- piglets than in the BMPR-IB-/746G piglets. Proteomic analysis identified 139 differentially expressed proteins (DEPs) in the hindlimb fibula of BMPR-IB-/746G piglets compared to the wild-type (WT) controls. Most DEPs are involved in skeletal or embryonic development and/or the TGF-β pathway and tumor progression. Gene Ontology (GO) and protein domain enrichment analysis suggested alterations in these processes. Of 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 development. Our study provides novel findings on the role of BMPR-IB in mammalian limb development.
  • #Authors contributed equally to this work
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