These mice carry an ENU-induced mutation characterized by a low frequency of revertants and a faint display of dystrophin immunofluorescence in skeletal sarcolemma and skeletal muscle.
Dr. Verne M. Chapman (deceased), Roswell Park Memorial Institute
Dmdmdx-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 Dmdmdx-4Cv and Dmdmdx-5Cv strains have 10 times fewer revertants than the Dmdmdx and Dmdmdx-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 Dmdmdx 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 Hprta and Pgk1a (both are on the X chromosome).
This strain was created in the laboratory of Verne M. Chapman. A C57BL/6Ros female (a subline of C57BL/6J) was crossed to a male of strain C3Ha.X25, a double congenic strain carrying Pgk1a (from a wild Mus musculus musculus mouse trapped in Denmark) and Hprta (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-Dmdmdx/+ 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-Dmdmdx/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 Dmdmdx-2-5Cv. Each of these new mutations was subsequently backcrossed onto C57BL/6Ros. The B6Ros.Cg-Dmdmdx-3Cv congenic was reported in publication to have reached generation N14 in 1993. In 1995 Verne Chapman sent homozygous females and hemizygous males to The Jackson Laboratory where they were bred to C57BL/6J for historectomy rederivation. The resulting offspring were sibling intercrossed to generate a homozygous line. In 2003 homozygous embryos at generation N1F13 were cryopreserved and in 2013 sperm was frozen from cryo-recovered hemizygous males.
|Allele Name||X linked muscular dystrophy 3, Verne Chapman|
|Allele Type||Chemically induced (ENU) (Hypomorph)|
|Allele Synonym(s)||mdx3cv; mdxcv3; mdx3cv; mdx3cv|
|Gene Symbol and Name||Dmd, dystrophin, muscular dystrophy|
|Strain of Origin||C3Ha.Cg-Hprta Pgk1a|
|Molecular Note||A T to A transversion creates a novel splice acceptor site 14 bp upstream of the natural site in exon 66. Splicing at this mutant site results in the inclusion of 14 bp of intronic sequence and shifts the reading frame of the encoded mRNA. While a low level of a smaller transcript is expressed from this allele, western blot analysis failed to detect any isoform of protein in various tissues from homozygous mutant mice (J:12150). However, a second report shows that the transcript generated by skipping exons 65 and 66 (D65/66) generates an in-frame transcript that produces low levels of dystrophin (J:250658).|
|Mutations Made By|| |
Dr. Verne Chapman (deceased), Roswell Park Memorial Institute
Shin JH, Hakim CH, Zhang K, Duan D. 2011. Genotyping mdx, mdx3cv, and mdx4cv mice by primer competition polymerase chain reaction. Muscle Nerve 43(2):283-6. [PubMed: 21254096]
When maintaining a live colony, these mice can be bred as homozygous females and hemizygous males (the gene is X linked).
When using the X linked muscular dystrophy 3, Verne Chapman mouse strain in a publication, please cite the originating article(s) and include JAX stock #002377 in your Materials and Methods section.