B6Ros.Cg-Dmd^mdx-2Cv/J

Stock number: 002388
Product name: X linked muscular dystrophy 2, Verne Chapman
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These mice carry an ENU-induced mutation characterized by a faint dystrophin immunofluorescence in skeletal sarcolemma and skeletal muscle in contrast to the other mutants which show no dystrophin reactivity.

Detailed description

Mice carrying the Dmd^mdx-2Cv mutation display a phenotype similar to the original Dmd^mdx mutation. Dmd^mdx-3Cv mutant mice display a faint dystrophin immunofluorescence in skeletal sarcolemma and skeletal muscle in contrast to the other mutants which show no dystrophin reactivity. This is similar to a group of human DMD patients. This mutant has a low frequency of revertants. The Dmd^mdx-4Cv and Dmd^mdx-5Cv strains have 10 times fewer revertants than the Dmd^mdx and Dmd^mdx-2Cv strains as viewed in quadricep cross-sections. This is not attributable to genetic background or viral infections. These reversion rate differences may be attributable to differences in the location of the point mutation. The large number of revertants in Dmd^mdx mutants has complicated the analysis of gene or cell therapies. These mutants are more useful for this purpose. All these strains are also hemizygous for Hprt^a and Pgk1^a (both are on the X chromosome).

Development

This strain was created in the laboratory of Verne M. Chapman. A C57BL/6Ros female was crossed to a male of strain C3Ha.X₂₅, a double congenic strain carrying Pgk1^a (from a wild Mus musculus musculus mouse trapped in Denmark) and Hprt^a (from Mus castaneus) on a C3H/HeHa background. F1 or F2 male progeny of this cross were treated with n-ethylnitrosourea (ENU) and crossed to C57BL/10Sn-Dmd^mdx/+ females. Female offspring of these crosses that exhibited consistently elevated plasma creatine kinase levels and that carried the X-chromosome markers of their mutagenized male progenitors were bred to C57BL/10Sn-Dmd^mdx/Y males. Transmission to male progeny of the elevated plasma CK phenotype and failure of the suspected new mutations at the Dmd locus to complement the classical mdx mutation identified four new mutations of Dmd, called Dmd^mdx-2-5Cv . Each of these new mutations was subsequently backcrossed onto C57BL/6Ros.

Allele

Symbol: Dmd^mdx-2Cv
Name: X linked muscular dystrophy 2, Verne Chapman
MGI accession ID: MGI:1856329
Generation method: Chemically induced (ENU)
Synonyms: mdx^2cv
Marker symbol: Dmd
Marker name: dystrophin, muscular dystrophy
Marker synonyms: BMD; CMD3B; DNADMD1; Dp427; Dp71; Duchenne muscular dystrophy; DXS142; DXS164; DXS206; DXS230; DXS239; DXS268; DXS269; DXS270; DXS272; dys; mdx; MRX85; pke; X-linked muscular dystrophy
Chromosome: X
Strain of origin: C3Ha.Cg-Hpr1t^a Pgk1^a
Molecular note: An A to T transversion two nucleotides 5' to the intron 42/exon 43 splice accesptor site. This mutation abolishes splicing at this site and induces aberrant splice products that do not preserve the reading frame.