Localization of the mdx mutation within the mouse dystrophin gene.

Abstract

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.

Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment

“…The molecular defect in the Mdm mdx murine mutation, causing premature termination of the 427 kDa dystrophin polypeptide, was included since Mdm mdx /Y mice are used as a model for human dystrophy. 23 In addition, we tested the platinum (Tyr cÀp ) mutation, an A-T substitution, changing a lysine residue at position 489 of tyrosinase to a termination codon. This tyrosinase truncation results in misrouting of the enzyme to the melanocyte periphery; thus, Tyr cÀp / Tyr cÀp homozygous mice have a white coat color, like albino homozygotes.…”

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

“…[1], [13], [14] Although the underlying gene defect is the same in human and the mdx mouse, the clinical picture is quite different. The mdx skeletal muscle undergoes an early acute phase of degeneration at about 3-4 weeks of age followed by a successful regeneration phase.…”

Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains

“…For instance, FVB/N mice are commonly used in conventional transgenesis (51), and 129 substrains have been used almost exclusively for the isolation of embryonic stem (ES) cells used for gene targeting (41,56). Alternatively, other inbred strains have found use as disease models due to naturally occurring mutations in genes linked to human disease (5,22,38,43). Even in the absence of engineered or known naturally occurring mutations, different inbred mouse strains can vary drastically in their susceptibility to clinically relevant diseases.…”