BMPR-IB gene disruption causes severe limb deformities in pigs

Area of Science:

• Genetics and Genomics
• Developmental Biology
• Molecular Biology

Background:

• The Bone Morphogenetic Protein Receptor Type IB (BMPR-IB) gene plays a critical role in skeletal development.
• Understanding BMPR-IB function is essential for addressing congenital limb malformations.

Purpose of the Study:

• To investigate the function of BMPR-IB in mammalian limb development using CRISPR/Cas9 gene editing.
• To characterize the phenotypic and molecular consequences of BMPR-IB disruption.

Main Methods:

• CRISPR/Cas9 gene editing was employed to generate BMPR-IB knockout piglets.
• Phenotypic analysis of limb morphology and skeletal structure was performed.
• Proteomic analysis (including Gene Ontology and protein domain enrichment) was conducted on hindlimb fibula samples.

Main Results:

• Unexpectedly generated homozygous (BMPR-IB-/-) and heterozygous (BMPR-IB-/746G) knockout piglets with complex genomic rearrangements.
• All BMPR-IB-disrupted piglets exhibited severe skeletal dysplasia, including limb deformities and inability to ambulate.
• Proteomic analysis identified 139 differentially expressed proteins (DEPs) in BMPR-IB-/746G piglets, many associated with skeletal development, TGF-β signaling, and tumor progression.

Conclusions:

• BMPR-IB is essential for normal mammalian limb development.
• Disruption of BMPR-IB leads to severe skeletal dysplasia and limb malformations.
• Altered protein expression profiles in BMPR-IB-disrupted piglets provide insights into the molecular mechanisms underlying skeletal development.