These Usp18 (or Ubp43)-mutant mice may be useful in studying interferons and their receptors, cellular function, signal transduction, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.
Dong-Er Zhang, University of California, San Diego
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Usp18 | ubiquitin specific peptidase 18 |
Homozygous Usp18 (or Ubp43) mutant mice on the FVB/N genetic background are viable and fertile, exhibiting none of the severe neurologic disorders that lead to embryonic lethality or early death reported for Ubp43-deficient mice on a C57BL/6 or mixed B6;129 genetic background. In contrast to wildtype mice, thymi from homozygous mice injected with LPS exhibit no protein from the targeted gene. Expression of the lacZ cassette is observed in both heterozygous and homozygous brain tissues. Homozygous mice are hypersensitive to type I interferon (IFN) and undergo apoptosis upon IFN stimulation. Ubp43-deficiency results in enhanced and prolonged STAT1 phosphorylation, DNA binding, and increased induction of hundreds of interferon stimulated genes (ISGs). Homozygous mice exhibit greater resistance to the cytopathic effects caused by a number of viruses (including lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and Sindbis virus (SNV)). Ubp43-deficient cells exhibit high levels of ISG15 modified proteins. These Usp18 (or Ubp43)-mutant mice may be useful in studying interferons and their receptors, cellular function, signal transduction, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector was designed to replace exons 2-4 of the targeted gene with a lacZ and PGK-neo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred with C57BL/6 to produce mutant mice. Next, these mice were backcrossed to FVB/N inbred mice for at least 10 generations prior to arrival at The Jackson Laboratory.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | Expression of lacZ is observed in brain tissues (expression in the ependymal cells of both the aqueduct and the ventricle). |
Allele Name | targeted mutation 1, Dong-Er Zhang |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | UBP43-; Usp18LacZ; Usp18tm1Dzh |
Gene Symbol and Name | Usp18, ubiquitin specific peptidase 18 |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | Expression of lacZ is observed in brain tissues (expression in the ependymal cells of both the aqueduct and the ventricle). |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 6 |
Molecular Note | Exons 2-4, which contain the translation initiation codon and Cys domain, were replaced with a neo-lacZ cassette via homologous recombination. Absence of gene expression in homozygous mutant animals was verified by Western blot analysis of LPS-stimulated thymus glands. |
Mutations Made By | Dong-Er Zhang, University of California, San Diego |
When maintaining a live colony, homozygous mice may be bred. The donating investigator reports that homozygous mice on the FVB/N genetic background exhibit none of the severe neurologic disorders that lead to the perinatal lethality observed in homozygotes on a C57BL/6 or mixed B6;129 genetic backgoround.
When using the FVB.129(B6)-Usp18tm1Dez/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007225 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Usp18<tm1Dzh> |
Frozen Mouse Embryo | FVB.129(B6)-Usp18<tm1Dez>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB.129(B6)-Usp18<tm1Dez>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB.129(B6)-Usp18<tm1Dez>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | FVB.129(B6)-Usp18<tm1Dez>/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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