Mice homozygous for the Utrntm1Jrs and Dmdmdx exhibit an onset of skeletal muscle dystrophy as early as 4 weeks of age and are a model for Duchenne Type Muscular Dystrophy.
Suzanne Berry, University of Illinois
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Dmd | dystrophin, muscular dystrophy |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Utrn | utrophin |
Mice homozygous for the Utrntm1Jrs and Dmdmdx alleles have a lifespan of 4 to 20 weeks, with only 50% surviving beyond 8 weeks of age. As early as 3 weeks of age homozygotes display growth delays, are smaller than wildtype controls and exhibit skeletal muscle dystrophy with abnormal waddling gait at 4 weeks of age. At 10 weeks of age, double mutants exhibit skeletal muscle degeneration, necrosis and interstitial fibrosis, as well as abnormal echocardiography results. By 15 weeks of age, the double homozygotes develop dilated cardiomyopathy. The double mutants exhibit kyphosis, compromised systolic and diastolic function, progressive fibrosis throughout the heart, cardiomyocyte membrane damage, ventricular cellular necrosis, and disorganized mitochondria and myofibrils in cardiomyocytes.
These double mutant mice were produced by breeding mice carrying the Utrntm1Jrs targeted mutation and the Dmdmdx spontaneous mutation.
To generate the Utrntm1Jrs targeted mutation, a targeting vector containing PGK-Neo cassette was used to disrupt an exon encoding the beginning of the cysteine-rich region of the protein. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The mice were maintained on a mixed B6;129 background.
The Dmdmdx spontaneous mutation arose just prior to 1977 at the Agricultural Research Council's Poultry Research Centre, U.K., in C57BL/10ScSn mice obtained from M. Festing (MRC Laboratory Animals Centre, Carshalton, Surrey, U.K.). Mice carrying the Dmdmdx allele were imported to The Jackson Laboratory in 1984 by Dr. Thomas Roderick, who received them from Dr. Karen Moore (Department of Genetics, University of California, Berkley). A C-to-T transition occurred at position 2983(ENSMUST00000114000 chrX:g.83803333 C>T; p.Q995*), resulting in a termination codon in place of a glutamine codon codon within exon 23 of the dystrophin muscular dystrophy gene (Dmd) on the X chromosome [note that Sicinski et al., 1989 originally reported termination codon at position 3185].
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. |
Allele Name | targeted mutation 1, Joshua R Sanes |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | uko; utrn- |
Gene Symbol and Name | Utrn, utrophin |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 10 |
Molecular Note | A neomycin resistance cassette replaced 2.7 kb of sequence including 52 bp of the exon that encodes the beginning of the C-terminal cysteine rich region. RT-PCR analysis demonstrated that a mutant transcript carrying the deletion was made in homozygous and heterozygous mice. Western blot analysis on extracts of muscle or lung tissue derived from homozygous mice confirmed that no detectable protein was expressed from this allele. |
When maintaining a live colony, mice carrying the Utrntm1Jrs allele alone can be bred as homozygotes.
When maintaining a live colony of mice carrying only the Dmdmdx allele, female mice homozygous for the Dmdmdx allele and male mice hemizygous for the Dmdmdx allele can be bred together.
When maintaining a live colony of mice carrying both mutations, female mice that are heterozygous for Utrntm1Jrs, homozygous for Dmdmdx can be bred to male mice that are hemizygous for Dmdmdx allele.
When using the mdx/utrn - mouse strain in a publication, please cite the originating article(s) and include JAX stock #016622 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Utrn<tm1Jrs>, Homozygous females and hemizyogus males for Dmd<mdx> |
Frozen Mouse Embryo | STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo | $3373.50 |
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.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.