The homologue of the Duchenne locus is defective in X-linked muscular dystrophy of dogs

Duchenne muscular dystrophy (DMD) is the most common and the most severe of the muscular dystrophies in man1. It is inherited as an X-linked recessive trait1 and is characterized by ongoing necrosis of skeletal muscle fibres with regeneration and eventually fibrosis and fatty infiltration2. Although the gene and gene product which are defective in DMD have recently been identified3–5, the pathogenesis of the disease is still poorly understood. A myopathy has been described in the dog6–8 which has been shown to be inherited as an X-linked trait9 and which is therefore a potential model of the human disease. We have studied the phenotypic expression of the disease, canine X-linked muscular dystrophy (CXMD), and have examined the molecular relationship between it and DMD. We report here that dogs with CXMD faithfully mimic the phenotype of Duchenne muscular dystrophy and that they lack the Duchenne gene transcript and its protein product, dystrophin.

[1]  K. Fischbeck,et al.  Duchenne muscular dystrophy gene expression in normal and diseased human muscle. , 1988, Science.

[2]  M. Koenig,et al.  Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals , 1987, Cell.

[3]  A. Monaco,et al.  Conservation of the Duchenne muscular dystrophy gene in mice and humans. , 1987, Science.

[4]  Eric P. Hoffman,et al.  Dystrophin: The protein product of the duchenne muscular dystrophy locus , 1987, Cell.

[5]  R. Waterston,et al.  Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. , 1988, The New England journal of medicine.

[6]  L. Duchen,et al.  The mutant mdx: inherited myopathy in the mouse. Morphological studies of nerves, muscles and end-plates. , 1987, Brain : a journal of neurology.

[7]  F. Mastaglia,et al.  Morphological changes in dystrophic muscle. , 1980, British medical bulletin.

[8]  D. Shotton,et al.  Muscular dystrophy in the mdx mouse: Histopathology of the soleus and extensor digitorum longus muscles , 1987, Journal of the Neurological Sciences.

[9]  A. Monaco,et al.  Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene , 1986, Nature.

[10]  K. Moore,et al.  X chromosome-linked muscular dystrophy (mdx) in the mouse. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Monaco,et al.  The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein , 1988, Cell.

[12]  A. D. Lahunta Veterinary neuroanatomy and clinical neurology. , 1977 .

[13]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[14]  Z. Kaprielian,et al.  Expression of fast and slow isoforms of the Ca2+-ATPase in developing chick skeletal muscle. , 1987, Developmental biology.

[15]  M. Brooke,et al.  Genetic heterogeneity in Duchenne Dystrophy , 1987, Annals of neurology.