Mice of this double mutant (targeted/spontaneous mutation) mouse strain exhibit a more severe dystrophic phenotype than single Dmdmdx mutants and may be useful in studies of neuromuscular junctions, and hereditary neuropathies, specifically Duchenne Type Muscular Dystrophy.
Kay Davies, University of Oxford
Female mice that are homozygous for the Utrntm1Ked allele and the Dmdmdx allele, and male mice that are homozygous for the Utrntm1Ked allele and hemizygous for the Dmdmdx allele, exhibit a more severe phenotype than single Dmdmdx mutants: earlier onset of muscle dystrophy (degeneration, macrophage infiltration and necrosis), weight loss after weaning, joint contractures, kyphosis, dystrophy of extraocular muscles, abnormal electrocardiograms, infertility and premature death. Growth retardation onset is at weaning. By 4 of 6 weeks of age, the double mutants exhibit reduced body weight, reduced mobility, abnormal breathing pattern and slack posture. Muscle weakness and kyphosis (curvature of the spine) is progressive and the double mutant mice develop a waddling gait. Necrosis of the diaphragm muscle is observed in 6 day old double mutant mice. Muscle fibers with centralized nuclei are seen in 2 week old double mutants. 8 to 10 week old mutants exhibit a muscular dystrophy phenotype similar to mice homozygous for the Dmdmdx allele with variation in muscle fiber size, necrosis, fibrosis, macrophage infiltration and centrally nucleated muscle fibers. Ultrastructural examination of postsynaptic motor endplate regions of neuromuscular and myotendinous junctions of the soleus and diaphragm muscle from 10 week old double mutant mice reveals a lack of junctional folds at the postsynaptic membrane. Female mice that are homozygous for the Utrntm1Ked allele and the Dmdmdx allele, and male mice that are homozygous for the Utrntm1Ked allele and hemizygous for the Dmdmdx allele, exhibit clinical symptoms as early as 4 weeks of age and die by 20 weeks of age.
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 the strain above. 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.
This double mutant strain was generated by crossing C57BL/10ScSn-Dmdmdx/J mice (Stock No. 001801) to STOCK Utrntm1Ked/J mice (Stock No. 013158).
The spontaneous mutation Dmdmdx 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 mdx 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).
For the Utrntm1Ked targeted mutation, a targeting vector containing a PGK-Neo cassette was used to disrupt exon 7. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+ derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to (DBA/2 X C57BL/6) F1 female mice. Heterozygotes were interbred to generate homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed to B6D2F1/J mice (Stock No. 100006) at least once to establish the colony.
|Allele Name||targeted mutation 1, Kay E Davies|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Kay E Davies; Utrntm1Ked|
|Gene Symbol and Name||Utrn, utrophin|
|Gene Synonym(s)||G-utrophin; DMDL; expressed sequence AA589569; dystrophin-like; AA589569; DRP; DRP1; Dmdl; Dmdl|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Insertion of a neomycin cassette into exon 7. No protein was detected in extracts derived from kidney, lung or brain of homozygous mice as assayed by Western blot analysis.|
|Mutations Made By|| |
Kay Davies, University of Oxford
|Allele Name||X linked muscular dystrophy|
|Allele Synonym(s)||Dmdmdx; X linked muscular dystrophy|
|Gene Symbol and Name||Dmd, dystrophin, muscular dystrophy|
|Gene Synonym(s)||Duchenne muscular dystrophy; CMD3B; DXS164; DXS230; DXS239; DXS268; DXS272; X-linked muscular dystrophy; BMD; pke; pke; DXS142; DXS206; DXS270; mdx; DXS269; MRX85; dys; X-linked muscular dystrophy; pyruvate kinase expression; Dp427; Dp71; mdx|
|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.|
Female mice that are homozygous for the Utrntm1Ked allele and the Dmdmdx allele, and male mice that are homozygous for the Utrntm1Ked allele and hemizygous for the Dmdmdx allele, exhibit clinical symptoms as early as 4 weeks of age and die by 20 weeks of age. When maintaining a live colony, female mice heterozygous for the Utrntm1Ked allele and the homozygous for the Dmdmdx allele can be crossed to male mice hemizygous for the Dmdmdx allele.
When using the utrn/mdx - mouse strain in a publication, please cite the originating article(s) and include JAX stock #014563 in your Materials and Methods section.
|Heterozygous or wild-type for Utrn<tm1Ked>, also Homozygous or Hemizygous for Utrn<tm1Ked>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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