Abstract
Epitope-specific monoclonal antibodies can provide unique insights for studying cellular proteins. Dystrophin is one of the largest cytoskeleton proteins encoded by 79 exons. The absence of dystrophin results in Duchenne muscular dystrophy (DMD). Over the last two decades, dozens of exon-specific human dystrophin monoclonal antibodies have been developed and successfully used for DMD diagnosis. Unfortunately, the majority of these antibodies have not been thoroughly characterized in dystrophin-deficient dogs, an outstanding large animal model for translational research. To fill the gap, we performed a comprehensive study on 65 dystrophin monoclonal antibodies in normal and dystrophic dogs (heart and skeletal muscle) by immunofluorescence staining and western blot. For comparison, we also included striated muscles from normal BL10 and dystrophin-null mdx mice. Our analysis revealed distinctive species, tissue and assay-dependent recognition patterns of different antibodies. Importantly, we identified 15 antibodies that can consistently detect full-length canine dystrophin in both immunostaining and western blot. Our results will serve as an important reference for studying DMD in the canine model.
Highlights
Duchenne muscular dystrophy (DMD) is an X-linked degenerative muscle disorder
To better characterize preclinical study in the canine model, we evaluated 65 dystrophin monoclonal antibodies in the heart and skeletal muscle of normal and dystrophic dogs by immunostaining and western blot
We evaluated 65 epitope-specific human dystrophin antibodies in dog and mouse muscle (Table S1)
Summary
Duchenne muscular dystrophy (DMD) is an X-linked degenerative muscle disorder It is caused by frame shift or frame interruption mutations of the dystrophin gene [1]. Dystrophin is predominantly expressed in skeletal and cardiac muscles [5]. It belongs to the b-spectrin/a-actinin protein family [6]. The first 240 amino acid residues form the actin-binding N-terminal domain. Dystrophin localizes to the cytoplasmic surface of the sarcolemma in striated muscles [8]. It establishes a mechanical link between the extracellular matrix and the actin cytoskeleton (reviewed in [9,10])
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