The systemic wrinkled skin phenotype involves aberrant expression and variation of genes related to the oxidative stress and extracellular matrix in Xiang pigs.

backgroundA phenotype characterized by age-dependent hairless, thicker and systemic wrinkled skin has been discovered from Chinese native Xiang pig herd, which is similar to the wrinkle skin phenotype and hereditary periodic fever syndrome observed in Shar-Pei dog. Our aim was to elucidate the functional mechanisms associated with these systemic wrinkle phenotype.

resultsGene expression changes in wrinkled skin were first explored via RNA-seq technology. There were 699 differentially expressed genes (DEGs) in wrinkled skin, with 272 downregulated genes and 427 upregulated genes. Most of the upregulated genes were significantly centered at pathways that generate reactive oxygen species (ROS), such as carbon and lipid metabolism, the citrate cycle and the oxidation-reduction process, leading to excessive ROS production and/or DNA damage in both the epidermal and dermal compartments of the skin. The downregulated genes were involved mainly in extracellular matrix (ECM) signaling. The most decreased genes were focused on several ECM components, including COL1A1, COL21A1, COL6A3, and ELN, likely related with ECM disorders. Moreover, 831 SVs and 26 CNVs were found in the gene regions of 335 DEGs according to the genomic resequencing data from the same wrinkled skin and control samples. These SVs and CNVs contributed to the deletion, insertion, duplication and inversion in exons, introns and regulatory regions of the DEGs. We then used F2 crossbreds by using Large White pig and the wrinkled Xiang pig as parents to verify the skin features and gene expression changes. Approximately 26% of F2 individuals exhibited a wrinkled skin phenotype, whereas the skin on F1 hybrids remained unchanged, suggesting autosomal recessive inheritance. The disorganized and thinner collagen bundles in the dermis of wrinkled skin were very similar to those of the parents, and many genes were shared between F2 pigs and the parents, including 137 DEGs corresponding to wrinkle scores, 23 oxidative stress-related genes, nine aging-related genes, and four ECM genes.

conclusionsThe systemic wrinkled skin phenotype of pigs involves aberrant gene expression and genetic variations related to oxidative stress and ECM components.