Effect of Zbed6 Single-Allele Knockout on the Growth and Development of Skeletal Muscle in Mice

Abstract

ZBED6, a key transcription factor, plays an important role in skeletal muscle and organ growth. ZBED6 knockout (ZBED6−/−) leads to the upregulation of IGF2 in pig and mice muscle, thereby increasing muscle mass. However, the effects and mechanism of Zbed6 single-allele knockout (Zbed6+/−) on mice muscle remain unknown. Here, we reported that Zbed6+/− promotes muscle growth by a new potential target gene rather than Igf2 in mice muscle. Zbed6+/− mice showed markedly higher muscle mass (25%) and a markedly higher muscle weight ratio (18%) than wild-type (WT) mice, coinciding with a larger muscle fiber area (28%). Despite a significant increase in muscle growth, Zbed6+/− mice showed similar Igf2 expression with WT mice, indicating that a ZBED6–Igf2-independent regulatory pathway exists in Zbed6+/− mice muscle. RNA-seq of muscle between the Zbed6+/− and WT mice revealed two terms related to muscle growth. Overlapping the DEGs and C2C12 Chip-seq data of ZBED6 screened out a potential ZBED6 target gene Barx2, which may regulate muscle growth in Zbed6+/− mice. These results may open new research directions leading to a better understanding of the integral functions of ZBED6 and provide evidence of Zbed6+/− promoting muscle growth by regulating Barx2 in mice.