In this strain a PGK-NEO cassette replaces the exon encoding the ATM kinase domain and the adjacent 3' exon of the Atm gene. Mice homozygous for this targeted mutation succumb to thymic lymphomas by 4 months of age, exhibit neurodegeneration and have applications in studies related to Ataxia-Telangiectasia.
Yang Xu, University of California, San Diego
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Atm | ataxia telangiectasia mutated |
The ATM protein is a DNA double-strand break sensor protein, delaying cell cycle by activating CHK2 checkpoint homolog or arresting cell cycle/initiate apoptosis by phosphorylating p53. These mice carry a targeted mutation of the Atm gene in which the exon encoding the ATM kinase domain and the adjacent 3' exon is disrupted by a PGK-NEO cassette. Mice that are homozygous for the allele are viable, but exhibit retarded growth, and are infertile due to meiotic failure. Homozygotes develop thymic lymphomas that eventually block the thoracic cavity and die before 4 months of age. Mutant mice have fewer pre-B cells and thymocytes, and lower IgG levels. Although ataxia is not observed, homozygotes develop neurodegeneration in the neocortex (large vacuoles in the cerebellar Purkinje cell layer). Heterozygotes are viable and fertile.
A targeting vector designed by Drs. Yang Xu and David Baltimore (Massachusetts Institute of Technology) containing a PGK-NEO cassette was inserted into position 5979, disrupting the exon encoding the ATM kinase domain and the adjacent 3' exon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric mice were bred to C57BL/6 mice. The mice were maintained on a mixed B6;129S4 background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
Allele Name | targeted mutation 1, David Baltimore |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | ATM- |
Gene Symbol and Name | Atm, ataxia telangiectasia mutated |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 9 |
Molecular Note | Part of an exon encoding the kinase-conserved sequence of Atm and the following 3' exon was replaced with a PGK-neomycin cassette. |
Homozygotes die by four months of age due to thymic lymphomas that block the thoracic cavity. When maintaining a live colony, heterozygous mice are bred with wildtype mice from the colony.
When using the ATM- mouse strain in a publication, please cite the originating article(s) and include JAX stock #020943 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Atm<tm1Bal> |
Frozen Mouse Embryo | B6;129S4-Atm<tm1Bal>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S4-Atm<tm1Bal>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S4-Atm<tm1Bal>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129S4-Atm<tm1Bal>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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