These mice possess loxP sites flanking exons 57 and 58 of the ataxia telangiectasia mutated homolog (human), Atm, gene and have applications in studies related to Ataxia-Telangiectasia, DNA double-strand-break repair, and DNA double-strand-break joining processes.
Dr. Frederick W. Alt, Children's Hospital
Yuko Fujiwara, Harvard Medical School
Phosphoinositide 3-kinaserelated protein kinase (PIKK) family member ATM (Ataxia-telangiectasia mutated) is activated by DNA double-strand breaks and regulates the DNA double-strand break response and repair. These mice possess loxP sites on either side of exons 57-58 of the targeted gene, which encode for the core PIKK kinase domain. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 57-58 deleted in the cre-expressing tissues.
Dr. Frederick W Alt, while at Harvard Medical School, designed a targeting vector containing a loxP flanked PGK-Neo cassette. This selection cassette was inserted downstream of exon 58 of the targeted gene, and another loxP site was inserted upstream of exon 57. This construct was electroporated into 129S6/SvEvTac derived
TC1 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the selection cassette but did retain the loxP-flanked exons 57 -58 were injected in blastocysts. The resulting mice were maintained by sibling intercrossing. A homozygous male was then bred to a 129S6/SvEvTac female. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.
|Allele Name||targeted mutation 2.1, Frederick W Alt|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Atm, ataxia telangiectasia mutated|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Sequence encoding the core PIKK kinase domain of the protein protein product were floxed by placing a loxP site upstream of exon 57 and floxed neomycin cassette downstream of exon 58. The neomycin cassette was subsequently removed by transient infection of cre recombinase.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Atmc mouse strain in a publication, please cite the originating article(s) and include JAX stock #021444 in your Materials and Methods section.