This double mutant (targeted/spontaneous mutation) mouse strain may be useful in studies of neuromuscular junctions, and hereditary neuropathies, specifically Duchenne Type Muscular Dystrophy.
Kay Davies, University of Oxford
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 as Stock No. 001801 in 1984 by Dr. Thomas Roderick, who received them from Dr. Karen Moore (Department of Genetics, University of California, Berkley). Upon arrival, some mice were bred to DBA/2J inbred mice (Stock No. 000671) using a marker-assisted, speed congenic approach to generate a DBA/2J-congenic strain.
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 as Stock No. 013158, the mice were crossed to B6D2F1/J mice (Stock No. 100006) at least once to establish the colony. Some mice were bred to DBA/2J inbred mice using a marker-assisted, speed congenic approach to generate a DBA/2J-congenic strain.
This double mutant strain (Stock No. 022506) was generated by crossing DBA/2J backcrossed Dmdmdx/J mice and Utrntm1Ked/J mice.
|Allele Name||X linked muscular dystrophy|
|Allele Synonym(s)||mdx; pke; pyruvate kinase expression|
|Gene Symbol and Name||Dmd, dystrophin, muscular dystrophy|
|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 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, Kay E Davies|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Utrn, utrophin|
|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
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 D2 utr/mdx mouse strain in a publication, please cite the originating article(s) and include JAX stock #022506 in your Materials and Methods section.