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
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|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Atf4 KO; Atf4-; Atf4tm1Tmt|
|Gene Symbol and Name||Atf4, activating transcription factor 4|
|Strain of Origin||129|
|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.
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