These mice carry a truncation mutation of the Atm, ataxia telangiectasia mutated homolog (human), gene. This mutant mouse strain may be useful in studies of ataxia telangiectasia, neurodevelopment and thymic lymphoma.
Michael Weil, Colorado State University
Mice homozygous for this targeted mutation display many of the characteristics of ataxia telangiectasia, including growth retardation, neurologic dysfunction, infertility, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation. Most homozygotes develop thymic lymphoma. Homozygotes are infertile. Heterozygous mice display no abnormalities through eight months of age and are more sensitive to ionizing radiation than wildtype mice. Fewer than expected homozygotes are produced from heterozygote X heterozygote crosses. This mutant mouse strain may be useful in studies of ataxia telangiectasia, neurodevelopment and thymic lymphoma.
This mutation was originally characterized on the 129S6/SvEvTac background. 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.
Importation of this model was supported by the A-T Children's Project.
A targeting vector containing neomycin resistance was used to disrupt a 178 bp exon. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J recipient blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTac mice, and then backcrossed to C57BL/6J mice using a speed congenic protocol for 5 generations and then conventionally backcrossed for an additional 2 generations.
|Allele Name||targeted mutation 1, Anthony Wynshaw Boris|
|Allele Type||Targeted (Null/Knockout, Humanized sequence)|
|Allele Synonym(s)||Atm-; ATM-; Atmins5790neo; Atmtm1Awbl|
|Gene Symbol and Name||Atm, ataxia telangiectasia mutated|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A PGK-neomycin cassette was inserted into position 5979 of the Atm gene. This mutation results in a truncated protein, and the position of the mutation corresponds to the location of truncation mutations known to exist in humans.|
|Mutations Made By|| |
Dr. Anthony Wynshaw-Boris, Case Western Reserve University, School of Medicine
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes are infertile. Fewer than expected homozygotes are produced from heterozygote X heterozygote crosses.
When using the ATM- mouse strain in a publication, please cite the originating article(s) and include JAX stock #008536 in your Materials and Methods section.