B6.129(Cg)-Gpx1^tm1Ysh/MgoldJ

Stock number: 023919
Product name: Gpx1-/-
Research areas: Cell Biology Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

This Gpx1 knockout strain is useful in studies of redox-mediated signaling and oxidative stress.

Detailed description

Gpx1 encodes an intracellular selenium-containing glutathione peroxidase that detoxifies hydrogen peroxide and is involved in regulation of redox-balance and redox-mediated signaling as well as protection against reactive oxygen species. These mice carry a targeted mutation in which exon 2 is replaced by a NEO cassette. Mice that are homozygous for this targeted mutation are viable and fertile. No gene product (mRNA) is detected by Northern blot analysis of brain, heart, kidney, liver, and lung tissue from homozygous mice. Glutathione peroxidase activity is not detected in brain tissue and is significantly reduced in lens, heart, liver and small intestine. Homozygotes exhibit increased sensitivity to noise, with 4 week old mutant mice exhibiting more severe cochlear hair cell and nerve fiber loss after noise exposure than wildtype controls. Reactive oxygen species levels are increased in the brains of knock out mice, which are also resistant to kainic acid induced seizures and neuron damage. Knock out mice are less susceptible to striatal dopaminergic nerve injury after 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treatment. Small intestine jejunum crypts regeneration is increased and ileal and jeunum crypts are more resistant to gamma radiation induced damage than wildtype controls. Knock out mice are more susceptible to myocarditis caused by coxsackievirus B3 infection. Arachidonic acid metabolism in mutant mice is impaired in platelets, which when incubated with arachidonic acid, produce decreased levels of 12-hydroxyeicosatetraenoic acid and more polar products when compared to wildtype controls. By 3 to 4 months of age, 13% of homozygous mice on the 129 background develop cataracts. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Development

A targeting vector designed by Dr. Ye-Shih Ho (Wayne State University) containing a NEO cassette was used to disrupt exon 2. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were crossed for approximately 6 generations to C57BL/6. Dr. Matthew Goldberg obtained the mice and backcrossed them to C57BL/6J for 3 or 4 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background. The mice were bred to two other targeted mutant lines on the congenic C57BL/6 background, with some 129 contribution. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to obtain this single mutant line.

Allele

Symbol: Gpx1^tm1Ysh
Name: targeted mutation 1, Ye-Shih Ho
MGI accession ID: MGI:2158814
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Gpx1-; GPX1 KO; GpX-1 KO; GSHPx-1-deficient
Marker symbol: Gpx1
Marker name: glutathione peroxidase 1
Marker synonyms: cellular GPx; CGPx; Gpx; GPx-1; GPXD; GSHPx; GSHPX1; GSHPx-1
Chromosome: 9
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Insertion of a neomycin resistance cassette disrupted exon 2 of the gene. Northern blots of total RNA isolated from brain, heart, kidney, liver, and lung of homozygous mutant mice showed no detectable transcript of the targeted gene when probed with an a gene-specific cDNA probe.