Overview

Also Known As:Pus1 knock-out

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).

Donating Investigator

Mark D Fleming, Children's Hospital Boston

Genetic overview

Genetic Background	Generation

Pus1^tm1.1Mdf

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Pus1	pseudouridine synthase 1

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Research Applications

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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 These mice carry a knock out mutation of the Pus1 gene, in which most of exon 3 has been replaced by an IRES-lacZ cassette.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.

Development

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-Hprt^b-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.

Selected References

Mangum JE; Hardee JP; Fix DK; Puppa MJ; Elkes J; Altomare D; Bykhovskaya Y; Campagna DR; Schmidt PJ; Sendamarai AK; Lidov HG; Barlow SC; Fischel-Ghodsian N; Fleming MD; Carson JA; Patton JR. 2016. Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations. Sci Rep 6:26202PubMed: 27197761 MGI: J:237107

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Genetics

Pus1^tm1.1Mdf

Allele Symbol: Pus1^tm1.1Mdf

Allele Name	targeted mutation 1.1, Mark D Fleming
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Pus1, pseudouridine synthase 1
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt^b-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.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

myopathy, lactic acidosis, and sideroblastic anemia

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Pus1^tm1.1Mdf/Pus1^tm1.1Mdf
B6.129S7(C)-Pus1

behavior/neurological phenotype

impaired exercise endurance
- mice fatigue more quickly in exercise treadmill test exhibiting a 46% decrease in run-to-fatigue time
- no difference in grip strength or rotorod speed/time as compared to controls

muscle phenotype

abnormal muscle physiology
- 38% decrease in high succinate dehydrogenase (SDH) activity myofibers
- 63% reduction in cytochrome c oxidase activity in red gastrocnemius muscle
- reduction in oxidative capacity of myofibers

decreased skeletal muscle fiber size
- 24% increase in mean cross-sectional myofiber area in the tibialis anterior muscle
- however, there are no changes in percentage of extracellular matrix area or centralized nuclei
- increase is only observed in myosin heavy chain IIB expressing fibers

decreased skeletal muscle mass
- females exhibit decreased muscle mass and a smaller gastrocnemius to body weight ratio at 7 weeks of age, however, by 14 weeks there is no significant difference

cellular phenotype

decreased mitochondria size
- 33% reduction in average mitochondrial size
- 45% reduction in mitochondrial density
- increase in number of very small mitochondria
- mitochondria are reduced in size in skeletal muscle, but not liver

growth/size/body region phenotype

slow postnatal weight gain
- females and males have a reduced body weight as compared to wild-type mice at 7 and 14 weeks of age, respectively, however, no significant difference is observed at later ages

homeostasis/metabolism phenotype

impaired exercise endurance
- mice fatigue more quickly in exercise treadmill test exhibiting a 46% decrease in run-to-fatigue time
- no difference in grip strength or rotorod speed/time as compared to controls

References

Mangum JE; Hardee JP; Fix DK; Puppa MJ; Elkes J; Altomare D; Bykhovskaya Y; Campagna DR; Schmidt PJ; Sendamarai AK; Lidov HG; Barlow SC; Fischel-Ghodsian N; Fleming MD; Carson JA; Patton JR. 2016. Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations. Sci Rep 6:26202PubMed: 27197761 MGI: J:237107

Additional - Pus1^tm1.1Mdf related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Pus1
- Probe:Pus1 Probe
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	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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Also Known As:Pus1 knock-out

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Pus1tm1.1Mdf

Allele Symbol: Pus1tm1.1Mdf

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Pus1tm1.1Mdf/Pus1tm1.1MdfB6.129S7(C)-Pus1

behavior/neurological phenotype

muscle phenotype

cellular phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional - Pus1tm1.1Mdf related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Pus1^tm1.1Mdf

Allele Symbol: Pus1^tm1.1Mdf

Genotype: Pus1^tm1.1Mdf/Pus1^tm1.1Mdf
B6.129S7(C)-Pus1

Additional - Pus1^tm1.1Mdf related