Description

Strain Information

Type Chemically Induced Mutation; Congenic; Mutant Strain; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Hemizygote         (Female x Male)   15-JUL-11 Species laboratory mouse Background Strain C57BL/6Ros Donor Strain C3Ha.X25 (Pgk1a Hprta ) Generation N12F17p+F4 (19-MAR-12) Generation Definitions   Donating Investigator Dr. Verne M. Chapman (deceased),   Roswell Park Memorial Institute

Description
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.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Dmd

017929	B10.Cg-Cmahtm1Avrk Dmdmdx/PtmJ
018018	B10ScSn.Cg-Prkdcscid Dmdmdx/J
002388	B6Ros.Cg-Dmdmdx-2Cv/J
002377	B6Ros.Cg-Dmdmdx-3Cv/J
002379	B6Ros.Cg-Dmdmdx-5Cv/J
001801	C57BL/10ScSn-Dmdmdx/J
013141	D2.B10-Dmdmdx/J
018915	STOCK Terctm1Rdp Dmdmdx/J
016622	STOCK Utrntm1Jrs Dmdmdx/J
014563	STOCK Utrntm1Ked Dmdmdx/J

View Strains carrying other alleles of Dmd     (10 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Cardiomyopathy, Dilated, 3b; CMD3B   (DMD) Muscular Dystrophy, Becker Type; BMD   (DMD) Muscular Dystrophy, Duchenne Type; DMD   (DMD)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Dmd^mdx-4Cv/Dmd^mdx-4Cv

        B6Ros.Cg-Dmd^mdx-4Cv

• muscle phenotype
• abnormal diaphragm morphology
  • mice exhibit fibrosis, fatty infiltration and necrosis in the diaphragm unlike in wild-type mice that increases with age   (MGI Ref ID J:23502)
• skeletal muscle fibrosis
  • mice exhibit progressive fibrosis of the diaphragm with age, unlike in wild-type mice   (MGI Ref ID J:23502)

Dmd^mdx-4Cv/Y

        B6Ros.Cg-Dmd^mdx-4Cv

• muscle phenotype
• abnormal diaphragm morphology
  • mice exhibit fibrosis, fatty infiltration and necrosis in the diaphragm unlike in wild-type mice that increases with age   (MGI Ref ID J:23502)
• skeletal muscle fibrosis
  • mice exhibit progressive fibrosis of the diaphragm with age, unlike in wild-type mice   (MGI Ref ID J:23502)

Dmd^mdx-4Cv/Y

        B6Ros.Cg-Dmd^mdx-4Cv/J

• muscle phenotype
• abnormal muscle contractility
  • highest specific tetanic force is lower than in wild-type mice   (MGI Ref ID J:134272)
  • at high frequencies mice titanic force is lower than in Dmd^mdx-3Cv mice   (MGI Ref ID J:134272)
  • following eccentric contraction damage, force is reduced to 20% of starting level unlike in wild-type mice that experience only a moderate drop in force   (MGI Ref ID J:134272)
  • age exacerbates force losses   (MGI Ref ID J:134272)
• abnormal skeletal muscle morphology
  • skeletal muscles exhibit variation in fiber size and centrally located nuclei unlike in wild-type mice   (MGI Ref ID J:134272)
  • mice exhibit macrophage invasion into muscles unlike in wild-type mice   (MGI Ref ID J:134272)
• • centrally nucleated skeletal muscle fibers   (MGI Ref ID J:134272)
  • increased variability of skeletal muscle fiber size   (MGI Ref ID J:134272)
• vision/eye phenotype
• abnormal eye electrophysiology
  • derived positive (P2) responses are delayed compared to in wild-type mice   (MGI Ref ID J:53822)
• behavior/neurological phenotype
• abnormal grip strength
  • mice exhibit weaker grip strength than Dmd^mdx-3Cv mice   (MGI Ref ID J:134272)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Dmd^mdx-4Cv/Dmd^mdx-4Cv

        involves: C3H/HeHa * C57BL/6Ros * C57BL/10Sn * M. m. castaneus * M. m musculus

• muscle phenotype
• abnormal skeletal muscle fiber morphology
  • skeletal muscle fibers undergo cycles of degeneration and regeneration accompanied by necrosis, fibrosis and centrally located nuclei   (MGI Ref ID J:128921)
• • centrally nucleated skeletal muscle fibers   (MGI Ref ID J:128921)
  • skeletal muscle fiber necrosis   (MGI Ref ID J:128921)
• increased satellite cell number   (MGI Ref ID J:128921)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Muscular Dystrophy
      Duchenne type

Dmd^mdx-4Cv related

Neurobiology Research
Muscular Dystrophy
      Duchenne type

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dmdmdx-4Cv
Allele Name		X linked muscular dystrophy 4, Verne Chapman
Allele Type		Chemically induced (ENU)
Common Name(s)		mdx4cv; mdx4cv; mdx4cv; mdxCv4;
Mutation Made By		Dr. Verne Chapman (deceased),   Roswell Park Memorial Institute
Strain of Origin		C3Ha.Cg-Hprt Pgk1
Gene Symbol and Name		Dmd, dystrophin, muscular dystrophy
Chromosome		X
Gene Common Name(s)		BMD; CMD3B; DXS142; DXS164; DXS206; DXS230; DXS239; DXS268; DXS269; DXS270; DXS272; Dp427; Dp71; Duchenne muscular dystrophy; X-linked muscular dystrophy; mdx; pke; pyruvate kinase expression;
Molecular Note		A C to T transition in exon 53 at position 7916 creates a premature stop codon. [MGI Ref ID J:34517]

Genotyping

Genotyping Information

Genotyping Protocols

Dmd^mdx-4Cv, Pyrosequencing

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]

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chapman VM; Miller DR; Armstrong D; Caskey CT. 1989. Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. Proc Natl Acad Sci U S A 86(4):1292-6. [PubMed: 2919177]  [MGI Ref ID J:9638]

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]  [MGI Ref ID J:169288]

Additional References

Danko I; Chapman V; Wolff JA. 1992. The frequency of revertants in mdx mouse genetic models for Duchenne muscular dystrophy. Pediatr Res 32(1):128-31. [PubMed: 1635838]  [MGI Ref ID J:23502]

Dmd^mdx-4Cv related

Adamo CM; Dai DF; Percival JM; Minami E; Willis MS; Patrucco E; Froehner SC; Beavo JA. 2010. Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy. Proc Natl Acad Sci U S A 107(44):19079-83. [PubMed: 20956307]  [MGI Ref ID J:166234]

Banks GB; Combs AC; Chamberlain JR; Chamberlain JS. 2008. Molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a truncated dystrophin. Hum Mol Genet 17(24):3975-86. [PubMed: 18799475]  [MGI Ref ID J:142565]

Chretien F; Dreyfus PA; Christov C; Caramelle P; Lagrange JL; Chazaud B; Gherardi RK. 2005. In vivo fusion of circulating fluorescent cells with dystrophin-deficient myofibers results in extensive sarcoplasmic fluorescence expression but limited dystrophin sarcolemmal expression. Am J Pathol 166(6):1741-8. [PubMed: 15920159]  [MGI Ref ID J:98788]

Claeys KG; Sozanska M; Martin JJ; Lacene E; Vignaud L; Stockholm D; Laforet P; Eymard B; Kichler A; Scherman D; Voit T; Israeli D. 2010. DNAJB2 expression in normal and diseased human and mouse skeletal muscle. Am J Pathol 176(6):2901-10. [PubMed: 20395441]  [MGI Ref ID J:161160]

Danko I; Chapman V; Wolff JA. 1992. The frequency of revertants in mdx mouse genetic models for Duchenne muscular dystrophy. Pediatr Res 32(1):128-31. [PubMed: 1635838]  [MGI Ref ID J:23502]

Gayraud-Morel B; Chretien F; Flamant P; Gomes D; Zammit PS; Tajbakhsh S. 2007. A role for the myogenic determination gene Myf5 in adult regenerative myogenesis. Dev Biol 312(1):13-28. [PubMed: 17961534]  [MGI Ref ID J:128921]

Howard PL; Dally GY; Wong MH; Ho A; Weleber RG; Pillers DA; Ray PN. 1998. Localization of dystrophin isoform Dp71 to the inner limiting membrane of the retina suggests a unique functional contribution of Dp71 in the retina. Hum Mol Genet 7(9):1385-91. [PubMed: 9700191]  [MGI Ref ID J:115134]

Im WB; Phelps SF; Copen EH; Adams EG; Slightom JL; Chamberlain JS. 1996. Differential expression of dystrophin isoforms in strains of mdx mice with different mutations. Hum Mol Genet 5(8):1149-53. [PubMed: 8842734]  [MGI Ref ID J:34517]

Judge LM; Haraguchiln M; Chamberlain JS. 2006. Dissecting the signaling and mechanical functions of the dystrophin-glycoprotein complex. J Cell Sci 119(Pt 8):1537-46. [PubMed: 16569668]  [MGI Ref ID J:107808]

Khouzami L; Bourin MC; Christov C; Damy T; Escoubet B; Caramelle P; Perier M; Wahbi K; Meune C; Pavoine C; Pecker F. 2010. Delayed cardiomyopathy in dystrophin deficient mdx mice relies on intrinsic glutathione resource. Am J Pathol 177(3):1356-64. [PubMed: 20696779]  [MGI Ref ID J:163690]

Laure L; Suel L; Roudaut C; Bourg N; Ouali A; Bartoli M; Richard I; Daniele N. 2009. Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling. FEBS J 276(3):669-84. [PubMed: 19143834]  [MGI Ref ID J:147891]

Li D; Shin JH; Duan D. 2011. iNOS Ablation Does Not Improve Specific Force of the Extensor Digitorum Longus Muscle in Dystrophin-Deficient mdx4cv Mice. PLoS One 6(6):e21618. [PubMed: 21738735]  [MGI Ref ID J:174763]

Li D; Yue Y; Duan D. 2008. Preservation of muscle force in mdx3cv mice correlates with low-level expression of a near full-length dystrophin protein. Am J Pathol 172(5):1332-41. [PubMed: 18385524]  [MGI Ref ID J:134272]

Li D; Yue Y; Lai Y; Hakim CH; Duan D. 2011. Nitrosative stress elicited by nNOSmicro delocalization inhibits muscle force in dystrophin-null mice. J Pathol 223(1):88-98. [PubMed: 21125668]  [MGI Ref ID J:167308]

Li S; Kimura E; Ng R; Fall BM; Meuse L; Reyes M; Faulkner JA; Chamberlain JS. 2006. A highly functional mini-dystrophin/GFP fusion gene for cell and gene therapy studies of Duchenne muscular dystrophy. Hum Mol Genet 15(10):1610-22. [PubMed: 16595609]  [MGI Ref ID J:144130]

Pillers DA; Weleber RG; Green DG; Rash SM; Dally GY; Howard PL ; Powers MR ; Hood DC ; Chapman VM ; Ray PN ; Woodward WR. 1999. Effects of dystrophin isoforms on signal transduction through neural retina: genotype-phenotype analysis of duchenne muscular dystrophy mouse mutants. Mol Genet Metab 66(2):100-10. [PubMed: 10068512]  [MGI Ref ID J:53822]

Tanaka KK; Hall JK; Troy AA; Cornelison DD; Majka SM; Olwin BB. 2009. Syndecan-4-expressing muscle progenitor cells in the SP engraft as satellite cells during muscle regeneration. Cell Stem Cell 4(3):217-25. [PubMed: 19265661]  [MGI Ref ID J:149919]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain is maintained by mating homozygous females to hemizygous males (X-linked).
Mating System	Homozygote x Hemizygote         (Female x Male)   15-JUL-11
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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