DMD(MDX-BETA-GEO) - A NEW ALLELE FOR THE MOUSE DYSTROPHIN GENE

During a gene trap screen, an insertion of the gene trap vector into t he dystrophin gene, creating a new allele for the Dmd gene, has been d iscovered. Because the ROSA beta geo vector was used, the new allele i s called Dmd(mdx-beta geo). The insertion occurred 3' of exon 63 of th e dystrophin gene, resulting in a mutation that affects all presently known dystrophin isoforms, In contrast to spontaneous or ENU-induced a lleles, Dmd(mdx-beta geo) can be used to follow dystrophin expression by staining for beta-galactosidase activity, The high sensitivity of t his method revealed additional and earlier expression of dystrophin du ring embryogenesis than that seen previously with other methods. Dystr ophin promoters are active predominantly in the dermamyotome, limb bud s, telencephalon, door plate, eye, liver, pancreas anlagen, and cardio vascular system. Adult Dmd(mdx-beta geo) mice show reporter gene expre ssion in brain, eye, liver, pancreas, and lung. In skeletal and heart muscle, beta-galactosidase activity is not detectable, confirming West ern blot data that indicate the absence of the mutant full-length prot ein in these tissues. Hemizygous Dmd(mdx-beta geo) mice show muscular dystrophy with degenerating muscle fibers, cellular infiltration, and regenerated muscle fibers that have centrally located nuclei. Some mut ant animals develop a dilated esophagus, probably due to constriction by the hypertrophic crura of the diaphragm. (C) 1998 Wiley-Liss, Inc.