B6-hMSTN (hGDF8) Mouse

The MSTN gene, also known as myostatin or growth differentiation factor 8 (GDF8), encodes a secreted protein belonging to the transforming growth factor-beta (TGF-β) superfamily ^[1]. Primarily expressed in skeletal muscle, with minor expression in mitochondria, myocardium, and brain tissue, MSTN encodes the myostatin protein, a key negative regulator of skeletal muscle development ^[1]. Myostatin, through autocrine and paracrine signaling, inhibits muscle cell proliferation and differentiation, thereby limiting excessive skeletal muscle growth and maintaining muscle mass homeostasis ^[1-4]. Thus, MSTN plays a critical role in regulating body muscle development and maintaining normal muscle mass ^[3]. Furthermore, myostatin is implicated in adipogenesis regulation, exerting an inhibitory effect on fat cell differentiation ^[2]. Mutations in MSTN are associated with myostatin-related muscle hypertrophy, characterized by significant increases in muscle volume and strength, typically without severe medical consequences ^[5]. Consequently, inhibitors targeting myostatin are considered potential therapeutic targets for diseases such as muscular dystrophy and sarcopenia, and have shown promise in improving metabolic syndrome ^[1-5].

The B6-hMSTN (hGDF8) mouse is a humanized model constructed using gene editing technology, where the mouse Mstn genomic DNA was replaced with the human MSTN genomic DNA . The murine signal peptide was preserved. This model can be used for studying the pathological mechanisms and therapeutic approaches of muscular dystrophy, sarcopenia and metabolic syndrome, and for the development of MSTN-targeted drugs.