Effects of maternal immunization against myostatin on skeletal muscle mass of offspring in mice

Thesis (M.S.)--University of Hawaii at Manoa, 2007.Includes bibliographical references (leaves 45-55).i, 92 leaves, bound ill. 29 cmMyostatin (growth & differentiation factor-8), a member of the transforming growth factor-β superfamily, is a potent negative regulator of skeletal muscle growth. Previous studies have demonstrated hypermuscularity being induced by the absence or suppression of functional myostatin and conversely, muscle atrophy upon myostatin overexpression or administration. These studies indicate that myostatin-blockade has potential applications in improving muscle mass in farm animals and in treating muscle atrophies in humans. Since immunoneutralization has been effective in inhibiting biological molecules, it was hypothesized that maternal immunization against myostatin in female mice might enhance muscle mass in offspring via myostatin-blockade in the developing embryos and neonates by maternally transferred anti-myostatin antibody. In this study, twenty reproducing, twelve week-old female mice were divided into four groups, and immunized against KLH (Control) or recombinant porcine mature myostatin (rMyo) or two different KLH-conjugated myostatin peptides (Myo-I and Myo-2). Animals were immunized subcutaneously with 0.2 mg of immunogen mixed in TiterMax® adjuvant. Two or three boosters were administered prior to mating to ensure that the immunized female mice had significant antibody titers against their respective immunogens in ELISA. Sera collected from 3-day old neonates demonstrated significant titers, confirming the maternal transfer of anti-myostatin antibodies to offspring. However, no significant effects of immunization on the body weights of offspring were observed during 8 weeks of growout period. The offspring of the Myo-2 group had significantly heavier gastrocnemius and triceps muscles at 8 weeks compared to the controls (P