These Pus1 knockout mice exhibit reduced exercise capacity and abnormalities in skeletal muscle. They are suitable for use in applications related to the study of Mitochondrial Myopathy with Sideroblastic Anemia (MLASA).
Mark D Fleming, Children's Hospital Boston
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Pus1 | pseudouridine synthase 1 |
Pseudouridine synthase 1 modifies RNA chain uridine residues to pseudouridine, and is involved in stability maintenance of tRNA. Mutations in the human PUS1 gene can be a cause of mitochondrial myopathy and sideroblastic anemia (MLASA1). These mice carry a knock out mutation of the Pus1 gene, in which most of exon 3 has been replaced by an IRES-lacZ cassette. Mice that are homozygous for the targeted mutation are viable. Fertility of homozygotes has not been determined by the Donating Investigator. No PUS1 pseudouridinylation enzyme activity is detected by reverse transcriptase (RT) primer-extension/CMCT assay analysis of total RNA from kidney tissue of homozygous mice. At 7 weeks of age homozygotes are approximately 20% smaller and exhibit reduced gastrocnemius to body weight ratio when compared to wildtype controls. By 14 weeks of age, while homozygotes display body weight and muscle mass similar to that observed in wildtype controls, exercise capacity is diminished. A 24% increase in cross section myofiber area of tibialis anterior muscle, abnormal skeletal muscle fiber type proportions, reduced muscle oxidative capacity and
a reduction in intermyofibrillar mitochondrial density and size in gastrocnemius muscle are also observed. The expression of the IRES-lacZ has not been examined.
A targeting vector containing IRES/lacZ sequence and floxed NEO cassette was used to disrupt almost all of exon 3. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2 derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were bred to C57BL/6J to achieve germline transmission. The mice were bred to B6.C-Tg(CMV-cre)1Cgn/J, (Stock No. 006054) mice to remove the floxed NEO cassette. The mice were then backcrossed to C57BL/6J for 15 generations.
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 1.1, Mark D Fleming |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Pus1, pseudouridine synthase 1 |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 5 |
Molecular Note | A targeting vector containing IRES/lacZ sequence and floxed NEO cassette was used to disrupt almost all of exon 3. Cre-mediated recombination removed the floxed neo cassette. The expression of the lacZ has not been examined. Quantitative RT-PCR studies of several tissues did not detect mRNA in homozygous mutant mice. |
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). While homozygotes are viable, fertility of homozygotes has not been determined by the Donating Investigator.
When using the Pus1 knock-out mouse strain in a publication, please cite the originating article(s) and include JAX stock #026621 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Pus1<tm1.1Mdf> |
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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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