Pleiotropic Gene <i>HMGA2</i> Regulates Myoblast Proliferation and Affects Body Size of Sheep

Uncovering genes associated with muscle growth and body size will benefit the molecular breeding of meat Hu sheep. <i>HMGA2</i> has proven to be an important gene in mouse muscle growth and is associated with the body size of various species. However, its roles in sheep are still limited. Using sheep myoblast as a cell model, the overexpression of <i>HMGA2</i> significantly promoted sheep myoblast proliferation, while interference with <i>HMGA2</i> expression inhibited proliferation, indicated by qPCR, EdU, and CCK-8 assays. Furthermore, the dual-luciferase reporter system indicated that the region NC_056056.1: 154134300-154134882 (-618 to -1200 bp upstream of the <i>HMGA2</i> transcription start site) was one of the habitats of the <i>HMGA2</i> core promoter, given the observation that this fragment led to a ~3-fold increase in luciferase activity. Interestingly, SNP rs428001129 (NC_056056.1:g.154134315 C>A) was detected in this fragment by Sanger sequencing of the PCR product of pooled DNA from 458 crossbred sheep. This SNP was found to affect the promoter activity and was significantly associated with chest width at birth and two months old, as well as chest depth at two and six months old. The data obtained in this study demonstrated the phenotypic regulatory role of the <i>HMGA2</i> gene in sheep production traits and the potential of rs428001129 in marker-assisted selection for sheep breeding in terms of chest width and chest depth.