Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a degenerative disorder of the skeletal muscle in human and is caused by mutations in the dystrophin gene. The mdx mouse is a spontaneous mutant and an animal model for DMD. It has a point mutation in exon 23 of the dystrophin gene that eliminates the expression of dystrophin. However, this mutation does not disrupt the expression of four other shorter isoforms that are also expressed from the dystrophin gene through differential promoter usage. We generated another mutant mouse by gene targeting. Exon 52 of the dystrophin gene was disrupted, because the deletion of this exon is known to result in the DMD phenotype in human. In this mouse (mdx52), Dp140 and Dp260, shorter dystrophin isoforms, were absent in addition to dystrophin. The skeletal muscles were hypertrophic and the histology exhibited variations in the fiber size with a necrotic and regenerating process. This mouse is thus considered to represent another model for DMD.