Myostatin DNA vaccine increases skeletal muscle mass and endurance in mice.
Myostatin is a transforming growth factor-beta family member that acts as a negative regulator of skeletal muscle growth. In mice, genetic disruption of the myostatin gene leads to a marked increase in body weight and muscle mass. Similarly, pharmacological interference with myostatin in vivo in mdx knockout mice results in a functional improvement of the dystrophic phenotype. Consequently, myostatin is an important therapeutic target for treatment of diseases associated with muscle wasting. To construct a therapeutic DNA vaccine against myostatin, we coupled the foreign, immunodominant T-helper epitope of tetanus toxin to the N terminus of myostatin, and BALB/c mice were immunized with the recombinant vector. Sera from vaccinated mice showed the presence of specific antibodies against the recombinant protein. In addition, body weight, muscle mass, and grip endurance of vaccinated mice were significantly increased. Our study provides a novel, pharmacological strategy for treatment of diseases associated with muscle wasting.
Tang
Liang
L
Biotechnology Center, Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, China. zhangyqh@fmmu.edu.cn
Yan
Zhen
Z
Wan
Yi
Y
Han
Wei
W
Zhang
Yingqi
Y
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood; D017951:Antigen Presentation; D001835:Body Weight; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000276:immunology; D055435:Myostatin; D009929:Organ Size; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D010807:Physical Endurance / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D018984:Epitopes, T-Lymphocyte; C525912:Mstn protein, mouse; D055435:Myostatin; D020648:Peptide Elongation Factor 1; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D016212:Transforming Growth Factor beta; D019444:Vaccines, DNA