FVB.129(B6)-Usp18^tm1Dez/J

Stock number: 007225
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools, Virology Research

Description

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.

Detailed description

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.

Development

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.

Allele

Symbol: Usp18^tm1Dez
Name: targeted mutation 1, Dong-Er Zhang
MGI accession ID: MGI:2387336
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Usp18
Marker name: ubiquitin specific peptidase 18
Chromosome: 6
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: 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).
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.