Overview

Also Known As:B10.Cmah-mdx

Cmah-mdx mice are useful for studying how human-like CMAH-deficiency accelerates the onset and severity of the Duchenne muscular dystrophy (DMD) seen in Dmd^mdx mice. Cmah-mdx mice better mimic the human disease than the current standard model, and thus provide a model for DMD where translational research will be more relevant to issues affecting humans with the disease.

Donating Investigator

Paul T. Martin, The Research Institute at Nationwide Children's Hospital

Genetic overview

Genetic Background	Generation

Dmd^mdx

Allele Type	Gene Symbol	Gene Name
Spontaneous	Dmd	dystrophin, muscular dystrophy

Cmah^tm1Avrk

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cmah	cytidine monophospho-N-acetylneuraminic acid hydroxylase

View Genetics

Research Applications

Cell Biology Research
Neurobiology Research
Sensorineural Research
Mouse/Human Gene Homologs
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Cmah-mdx mutant mice harbor two mutations; the Cmah knockout allele (Cmah^tm1Avrk) and the spontaneous X-linked muscular dystrophy mutation (Dmd^mdx). The Cmah knockout allele abolishes Cmah expression; eliminating biosynthesis of N-glycolylneuraminic acid (Neu5Gc) from all cells and mimicking the normal human lack of functional CMAH.
The Dmd^mdx mutation abolishes dystrophin expression and models Duchenne muscular dystrophy (DMD) with less severe myopathology.

Compared to homozygous mdx mice (Dmd^mdx/mdx females / Dmd^mdx/Y males), Cmah-deficiency in homozygous Cmah-mdx mice (Cmah^-/-;Dmd^mdx/mdx females / Cmah^-/-;Dmd^mdx/Y males) results in accelerated age of onset, rate of progression, and severity of the major DMD phenotypes contributing to morbidity and mortality. This is especially true for loss of ambulation, cardiac and respiratory muscle weakness, and loss of lifespan. Homozygous Cmah-mdx mice also exhibit diminished expression/function of the dystrophin-associated glycoprotein (DAG) complex and increased activation of complement. Specifically, homozygous Cmah-mdx mice have Neu5Gc accumulation into small regenerating muscles in dystrophic regions. Some homozygous Cmah-mdx mice exhibit serum antibodies to Neu5Gc and increased classical complement Neu5Gc-dependent killing of muscle cells. The donating investigator reports one can successfully breed Cmah^-/-;Dmd^mdx/mdx females with Cmah^-/-;Dmd^mdx/Y males if the mice are young (starting at 6-8 weeks old).

Heterozygous Cmah-mdx mice (Cmah^+/-;Dmd^mdx/mdx females / Cmah^+/-;Dmd^mdx/Y males) are viable and fertile. The donating investigator reports heterozygous Cmah-mdx mice exhibit the same phenotypic traits as homozygous mdx mice (Dmd^mdx/mdx females / Dmd^mdx/Y males).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for these mice. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available. To view the phenotype describing the Cmah knockout mice a C57BL/6 genetic background, please see Stock No. 017588. To view the phenotype describing the mdx mutant mice on a C57BL/10ScSn genetic background, please see Stock No. 001801.

Development

These Cmah-mdx mutant mice harbor two mutations; the Cmah knockout allele (Cmah^tm1Avrk) and the spontaneous X-linked muscular dystrophy mutation (Dmd^mdx).

The Cmah knockout allele was designed by Dr. Ajit Varki (University of California San Diego) to have human-like inactivation of CMAH function via deletion of exon 6. Mice harboring the Cmah knockout allele (on a C57BL/6 congenic background) are described and available from The Jackson Laboratory Repository as Stock No. 017588.

C57BL/10ScSn mice harboring the spontaneous X-linked muscular dystrophy mdx allele are described and available from The Jackson Laboratory Repository as Stock No. 001801.

To generate this Cmah-mdx mutant line, Dr. Paul T. Martin (The Research Institute at Nationwide Children's Hospital, Columbus Ohio) bred C57BL/6 congenic Cmah^-/- males with C57Bl/10ScSn-Dmd^mdx/mdx females. The resulting male offspring (F1; Cmah^+/-;Dmd^mdx/Y) were bred with C57Bl/10ScSn-Dmd^mdx/mdx females to create F2 generation mice that were all dystrophin-deficient. The Cmah-mdx colony was then maintained by breeding Cmah^+/-;Dmd^mdx/Y males with C57Bl/10ScSn-Dmd^mdx/mdx females for more than ten generations. The Cmah-mdx colony was then maintained by breeding Cmah^-/-;Dmd^mdx/mdx females with Cmah^-/-;Dmd^mdx/Y males prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred with C57BL/10ScSnJ inbred mice (Stock No. 000476) for at least one generation to establish The Jackson Laboratory Repository colony.

Control Suggestions

Depending upon the nature of the experiment, the following mouse line(s) may be appropriate: Dmd^mdx mice (Stock No. 001801) and/or Cmah^tm1Avrk mice (Stock No. 017588).
000476 C57BL/10ScSnJ

Additional Information

Considerations for Choosing Controls

Selected References

Chandrasekharan K; Yoon JH; Xu Y; deVries S; Camboni M; Janssen PM; Varki A; Martin PT. 2010. A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy. Sci Transl Med 2(42):42ra54PubMed: 20668298 MGI: J:164594

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Genetics

Dmd^mdx

Allele Symbol: Dmd^mdx

Allele Name	X linked muscular dystrophy
Allele Type	Spontaneous
Allele Synonym(s)	mdx; pke; pyruvate kinase expression
Gene Symbol and Name	Dmd, dystrophin, muscular dystrophy
Gene Synonym(s)
Strain of Origin	C57BL/10ScSn
Chromosome	X
Molecular Note	This mutation arose in 1981 in a C57BL/10ScSn colony at University of Leicester. A C-to-T substitution in the CAA codon in exon 23 (ENSMUST00000114000 chrX:g.83803333C>T; c.2983C>T; p.Q995*) results in a termination codon (TAA) in place of a glutamine codon. This allele is predicted to produce a truncated protein.

Cmah^tm1Avrk

Allele Symbol: Cmah^tm1Avrk

Allele Name	targeted mutation 1, Ajit Varki
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Cmah^-
Gene Symbol and Name	Cmah, cytidine monophospho-N-acetylneuraminic acid hydroxylase
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	13
Molecular Note	Exon 6 and a floxed TK/neo were removed via transient cre mediated recombination.
Mutations Made By	Ajit Varki, University of California, San Diego

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cell Biology Research
- Signal Transduction
- Protein Processing
- Channel and Transporter Defects
Neurobiology Research
- Muscular Dystrophy
  - Duchenne type
- Channel and Transporter Defects
- Ataxia (Movement) Defects
Developmental Biology Research
- Mesodermal Defects
  - Myogenesis Defects
Mouse/Human Gene Homologs
- muscular dystrophy (Duchenne and Becker)

Genotype: Dmd^mdx related

Sensorineural Research
- Cataracts
Mouse/Human Gene Homologs
- muscular dystrophy (Duchenne and Becker)
Cell Biology Research
- Signal Transduction
Neurobiology Research
- Muscular Dystrophy
  - Duchenne type

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Cmah^tm1Avrk/Cmah^tm1Avrk Dmd^mdx/Dmd^mdx
involves: 129X1/SvJ * C57BL/10ScSn

behavior/neurological phenotype

abnormal gait
- at 8 months to a greater extent than in Dmd^mdx homozygotes

impaired coordination
- at 8 months on a rotarod to a greater extent than in Dmd^mdx homozygotes

muscle phenotype

cardiac muscle necrosis
- by 3 months, mice exhibit necrotic foci in the heart unlike wild-type mice

dystrophic muscle
- more severe than in Dmd^mdx homozygotes

muscle weakness
- at 8 months, mice exhibit impaired diaphragm and cardiac peak force compared with Dmd^mdx homozygotes

skeletal muscle fibrosis
- fibrosis in the diaphragm is increased compared to in Dmd^mdx homozygotes
- in the quadriceps at 6 weeks of age

cardiovascular system phenotype

cardiac muscle necrosis
- by 3 months, mice exhibit necrotic foci in the heart unlike wild-type mice

cellular phenotype

cardiac muscle necrosis
- by 3 months, mice exhibit necrotic foci in the heart unlike wild-type mice

hematopoietic system phenotype

increased macrophage cell number
- in muscles compared to in Dmd^mdx homozygotes

increased monocyte cell number
- in muscles compared to in Dmd^mdx homozygotes

immune system phenotype

increased macrophage cell number
- in muscles compared to in Dmd^mdx homozygotes

increased monocyte cell number
- in muscles compared to in Dmd^mdx homozygotes

mortality/aging

premature death
- 50% of mice dying by 11 months of age
- mice exhibit decreased life span compared with Dmd^mdx homozygotes

References

Chandrasekharan K; Yoon JH; Xu Y; deVries S; Camboni M; Janssen PM; Varki A; Martin PT. 2010. A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy. Sci Transl Med 2(42):42ra54PubMed: 20668298 MGI: J:164594

Additional - Cmah^tm1Avrk related

Additional - Dmd^mdx related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:DmdEnd Point
- Separated PCR:Cmah
- Standard PCR:Cmah
- Genotyping resources and troubleshooting
Breeding Considerations

The Dmd^mdx mutation is X-linked. When maintaining a live Cmah-mdx colony, females heterozygous for the Cmah knockout allele and homozygous for the X-linked mdx allele may be bred with males heterozygous for the Cmah knockout allele and hemizygous for the X-linked mdx allele. That is, Cmah^+/-;Dmd^mdx/mdx females may be bred with Cmah^+/-;Dmd^mdx/Y males. The donating investigator reports one can successfully breed Cmah^-/-;Dmd^mdx/mdx females with Cmah^-/-;Dmd^mdx/Y males if the mice are young (starting at 6-8 weeks old).
- Additional Breeding and Husbandry Support
Citation
When using the B10.Cmah-mdx mouse strain in a publication, please cite the originating article(s) and include JAX stock #017929 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Cmah<tm1Avrk>, X linked Heterozygous females and wildtype males for Dmd<mdx>, 1 pair minimum

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As:B10.Cmah-mdx

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Dmdmdx

Allele Symbol: Dmdmdx

Cmahtm1Avrk

Allele Symbol: Cmahtm1Avrk

Disease Terms

Research Areas By Phenotype

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

Genotype: Dmdmdx related

Mammalian Phenotype Terms by Genotype

Genotype: Cmahtm1Avrk/Cmahtm1Avrk Dmdmdx/Dmdmdxinvolves: 129X1/SvJ * C57BL/10ScSn

behavior/neurological phenotype

muscle phenotype

cardiovascular system phenotype

cellular phenotype

hematopoietic system phenotype

immune system phenotype

mortality/aging

References

Additional - Cmahtm1Avrk related

Additional - Dmdmdx related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Dmd^mdx

Allele Symbol: Dmd^mdx

Cmah^tm1Avrk

Allele Symbol: Cmah^tm1Avrk

Genotype: Dmd^mdx related

Genotype: Cmah^tm1Avrk/Cmah^tm1Avrk Dmd^mdx/Dmd^mdx
involves: 129X1/SvJ * C57BL/10ScSn

Additional - Cmah^tm1Avrk related

Additional - Dmd^mdx related