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
|Allele Type||Gene Symbol||Gene Name|
|Spontaneous||Dmd||dystrophin, muscular dystrophy|
|Allele Type||Gene Symbol||Gene Name|
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 3185, resulting in a termination codon in place of a glutamine codon.
|Allele Name||X linked muscular dystrophy|
|Allele Synonym(s)||mdx; pke; pvruvate kinase expression|
|Gene Symbol and Name||Dmd, dystrophin, muscular dystrophy|
|Gene Synonym(s)||BMD; CMD3B; DXS142; DXS164; DXS206; DXS230; DXS239; DXS268; DXS269; DXS270; DXS272; Dp427; Dp71; Duchenne muscular dystrophy; MRX85; X-linked muscular dystrophy; X-linked muscular dystrophy; dys; mdx; mdx; pke; pke; pyruvate kinase expression|
|Strain of Origin||C57BL/10ScSn|
|Molecular Note||This mutation arose in 1981 in a C57BL/10ScSn colony at University of Leicester. A C-to-T transition occurred at position 3185, resulting in a termination codon in place of a glutamine codon. This mutation 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)||AA589569; DMDL; DRP; DRP1; Dmdl; Dmdl; G-utrophin; dystrophin-like; expressed sequence AA589569|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|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.
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