Localization of the mdx mutation within the mouse dystrophin gene.

We have mapped human and mouse X chromosome-specific genomic and cDNA probes through an interspecies Mus musculus/spretus pedigree which contains the mdx mutation. The positions of these markers relative to one another and to the mdx mutation were delineated. Using probes corresponding to segments of the human Duchenne muscular dystrophy (DMD) gene transcript, the position of a cross-hybridizing mouse equivalent gene (mDMD) was located. In more than 200 animals mapped, three were identified which show recombination within this mDMD gene. Analysis of these three animals shows that the mDMD gene is oriented with its 5' end centromeric and its 3' end telomeric on the mouse X chromosome. Furthermore, their recombinational breakpoints are on either side of the mdx mutation, thus providing the first unequivocal demonstration that the mdx mutation is located within the mDMD gene and defining limits within that gene between which the mutation must lie. Within that segment the evidence indicates that there is no major deletion of an exon as detectable by Southern blot analysis in mdx animals. The mdx mouse becomes important as an animal model for the study of the expression of the DMD gene and its developmental consequences, for transgenic and other corrective manipulations.