A X chromosome-linked mouse mutant (mdx) has been identified that exhibits elevated plasma levels of muscle creatine kinase and pyruvate kinase, along with histological lesions characteristic of muscular dystrophy. The mutants show mild clinical symptoms and are viable and fertile. Linkage analysis with four X chromosome loci indicates that mdx maps in the Hq Bpa region of the mouse X chromosome, giving a gene order of mdx-Tfm-Pgk-1-Ags, the same as for the equivalent genes on the human X chromosome. There are two major forms of X chromosome-linked muscular dystrophy in humans: Duchenne and Becker. Recent linkage analyses suggest they could be allelic. However, the primary lesion and a homologous animal model are unknown for neither syndrome. Several mouse mutants exhibit myopathies, with the most investigated being the autosomal dy and dy2J mutants. There is controversy over whether these mutants are myogenic or neurogenic in origin, and thus their suitability as animal models for Duchenne/Becker muscular dystrophy is uncertain. It is of considerable interest that a spontaneous mutation (mdx) arose in an inbred C57BL/10 colony of mice that is X chromosome-linked and produces viable homozygous animals with high serum levels of muscle enzymes and histological lesions similar to human muscular dystrophy. The mdx mutation is X chromosome-linked and shows a recessive inheritance pattern. Biochemical analysis indicated that the variant enzyme had altered electrophoretic mobility, Km for phosphoenolpyruvate, resistance to trypsin digestion, and interaction with fructose diphosphate, suggesting a tissue-specific mutant affecting post-translational modification of the enzyme. This was resolved when it was realized that these biochemical characteristics were identical to those of the muscle-type isoenzyme coded for by the Pk-3 locus. Histological analysis of mutant and normal mice showed myopathic lesions similar to those of muscular dystrophy. The mdx mutant has an acquired, progressive, degenerative myopathy that is X chromosome-linked and probably myogenic in origin. The histological features, linkage, and map position of mdx make it worthy of more detailed examination as a potential animal model of X chromosome-linked muscular dystrophy. The gene order on the mouse X chromosome is mdx-Tfm-Pgk-1-Ags, similar to the order of Duchenne/Becker muscular dystrophy with the homologous genes on the human X chromosome.A X chromosome-linked mouse mutant (mdx) has been identified that exhibits elevated plasma levels of muscle creatine kinase and pyruvate kinase, along with histological lesions characteristic of muscular dystrophy. The mutants show mild clinical symptoms and are viable and fertile. Linkage analysis with four X chromosome loci indicates that mdx maps in the Hq Bpa region of the mouse X chromosome, giving a gene order of mdx-Tfm-Pgk-1-Ags, the same as for the equivalent genes on the human X chromosome. There are two major forms of X chromosome-linked muscular dystrophy in humans: Duchenne and Becker. Recent linkage analyses suggest they could be allelic. However, the primary lesion and a homologous animal model are unknown for neither syndrome. Several mouse mutants exhibit myopathies, with the most investigated being the autosomal dy and dy2J mutants. There is controversy over whether these mutants are myogenic or neurogenic in origin, and thus their suitability as animal models for Duchenne/Becker muscular dystrophy is uncertain. It is of considerable interest that a spontaneous mutation (mdx) arose in an inbred C57BL/10 colony of mice that is X chromosome-linked and produces viable homozygous animals with high serum levels of muscle enzymes and histological lesions similar to human muscular dystrophy. The mdx mutation is X chromosome-linked and shows a recessive inheritance pattern. Biochemical analysis indicated that the variant enzyme had altered electrophoretic mobility, Km for phosphoenolpyruvate, resistance to trypsin digestion, and interaction with fructose diphosphate, suggesting a tissue-specific mutant affecting post-translational modification of the enzyme. This was resolved when it was realized that these biochemical characteristics were identical to those of the muscle-type isoenzyme coded for by the Pk-3 locus. Histological analysis of mutant and normal mice showed myopathic lesions similar to those of muscular dystrophy. The mdx mutant has an acquired, progressive, degenerative myopathy that is X chromosome-linked and probably myogenic in origin. The histological features, linkage, and map position of mdx make it worthy of more detailed examination as a potential animal model of X chromosome-linked muscular dystrophy. The gene order on the mouse X chromosome is mdx-Tfm-Pgk-1-Ags, similar to the order of Duchenne/Becker muscular dystrophy with the homologous genes on the human X chromosome.