In this strain, a neomycin phosphotransferase resistance (neo) cassette replaces the entire coding region of the endogenous mouse activating transcription factor 4 (Atf4) gene, abolishing gene function. These mice may be useful for studying cell proliferation defects associated with blindness, osteoporosis, and stress responses.
Dr. Tim Townes, University of Alabama at Birmingham
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Atf4 | activating transcription factor 4 |
In this strain, a neomycin phosphotransferase resistance (neo) cassette replaces the entire coding region of the endogenous mouse activating transcription factor 4 (Atf4) gene, abolishing gene function. Mice homozygous for the Atf4 allele exhibit low viability, with delayed bone formation during embryonic development and low bone mass throughout postnatal life. They exhibit a reduction in oxidative stress-induced gene expression, resistance to oxidative death, and decreased consumption of the antioxidant glutathione. They also have decreased insulin sensitivity, smaller fat pads, and delayed hair growth as compared with control mice. Adults are severely microphthalmic, with no recognizable lens, anterior chamber, iris, or vitreous body. These mice may be useful for studying cell proliferation defects associated with blindness, osteoporosis, and stress responses.
A targeting vector was designed to replace exons 2-3 encoding the activating transcription factor 4 (Atf4) gene with a neomycin phosphotransferase resistance (neo) cassette. The construct was electroporated into either (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells or 129P2/OlaHsd-derived HM1 ES cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to Black Swiss mice. Subsequently, these mice were bred to C57BL/6 mice to generate a colony of Atf4-/- mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Allele Name | targeted mutation 1, Timothy Townes |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Atf4 KO; Atf4-; Atf4tm1Tmt |
Gene Symbol and Name | Atf4, activating transcription factor 4 |
Gene Synonym(s) | |
Strain of Origin | 129 |
Chromosome | 15 |
General Note | ES cell line = HM1 (129P2/OlaHsd-Hprtb-m3) or R1 ((129X1/SvJ x 129S1/Sv)F1-Kitl+). The data presented in J:74479 were obtained using R1 ES cells, though the authors report that they also generated mice with targeted alleles using HM1 ES cells. |
Molecular Note | Exons 2 and 3, comprising the entire coding region, were replaced with a targeting construct containing a neomycin resistance gene. Expression analysis confirmed the absence of transcript in homozygous mutant mice. |
Mutations Made By | Dr. Tim Townes, University of Alabama at Birmingham |
When maintaining a live colony, heterozygous mice may be bred to wildtype littermates. The Donating Investigator confirms homozygous lethality on a 129 background in addition it has been the experience of the Jackson Laboratory that Atf4 homozygous mutants are not generated from heterozygous matings on this mixed genetic background.
When using the STOCK Atf4tm1Tow/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013072 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wildtype for Atf4<tm1Tow> |
Frozen Mouse Embryo | STOCK Atf4<tm1Tow>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Atf4<tm1Tow>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Atf4<tm1Tow>/J | $3373.50 |
Frozen Mouse Embryo | STOCK Atf4<tm1Tow>/J | $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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