Large-scale analysis of differential gene expression in the hindlimb muscles and diaphragm of mdx mouse

The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD), whi ch is caused by the absence of dystrophin. Mdx limb muscles substantially c ompensate for the lack of dystrophin while the diaphragm is affected like D MD skeletal muscles. To understand better the complex cascade of molecular events leading to muscle degeneration and compensatory processes in mdx mus cles, we analyzed alterations of gene expression in mdx hindlimb and diaphr agm muscles as compared to their normal counterparts. The strategy was base d on suppression subtractive hybridization followed by reverse Northern qua ntitative hybridization. Four subtracted/normalized libraries, containing c DNA clones up- or downregulated in mdx hindlimb muscles or diaphragm, were constructed and a total of 1536 cDNA clones were analyzed. Ninety-three cDN As were found to be differentially expressed in mdx hindlimb muscles and/or diaphragm. They corresponded to 54 known genes and 39 novel cDNAs. The pot ential role of the known genes is discussed in the context of the mdx pheno type. (C) 2000 Elsevier Science B.V. All rights reserved.