Strain Name:

B6.Cg-Park7tm1Shn Gpx1tm1Ysh Park2tm1Shn/MgoldJ

Stock Number:

023968

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Availability:

Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 23-MAR-15
Use Restrictions Apply, see Terms of Use
This triple knockout strain is useful in studies of dopaminergic neuron physiology, regulation of striatal dopamine and serotonin, and Parkinson's disease.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemFemale Homozygous for Park7tm1Shn, Homozygous for Gpx1tm1Ysh, Homozygous for Park2tm1Shn x Male Homozygous for Park7tm1Shn, Homozygous for Gpx1tm1Ysh, Homozygous for Park2tm1Shn
Specieslaboratory mouse
GenerationN9+pN1 (13-FEB-14)
Generation Definitions
 
Donating Investigator Matthew Goldberg,   University of Texas Southwestern Medical Center at Dallas

Description
In the brains of patients with Parkinson's disease, the antioxidant enzyme glutathione peroxidase 1 activity level is diminished. Mutations in human PARK7 and PARK2 resulting loss of function have been linked to types of autosomal recessive Parkinson's disease. These mice carry targeted mutations for the Park7, Gpx1 and Park2 genes. Mice that are homozygous for all 3 of the targeted mutations are viable and fertile. In triple mutant mice, 12 to 18 months of age, striatal dopamine and serotonin levels are elevated, but with normal nigral neuron numbers. Parkin-/- DJ-1-/- Gpx1-/- exhibit enhanced motor behavior and are able to outperform wildtype controls in the rotarod test. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Development
For the Park7 allele, a targeting vector designed by Dr. Jie Shen (Brigham & Women's Hospital, Harvard University) containing a PGK-neomycin cassette was used to disrupt exon 2. The construct was electroporated into (C57BL/6 x 129)F1 derived MKV6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were backcrossed to C57BL/6J for 10 generations.

For the Gpx1tm1Ysh allele, 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.

For the Park2 allele, a targeting vector designed by a targeting vector designed by Dr. Jie Shen (Brigham & Women's Hospital, Harvard University) containing an in-frame EGFP coding sequence (followed by translation and transcription termination sequences and a PGK-neomycin cassette) was used to disrupt most of exon 3. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were backcrossed to C57BL/6J for 10 generations.

To generate this triple mutant strain, the Park7 and Park2 knockout lines were bred and intercrossed to obtain double knockout mice. The double knockout mice were then crossed to the Gpx1 knockout mice for 2 generations, and then intercrossed to obtain mice homozygous for all 3 alleles, Parkin-/- DJ-1-/- Gpx1-/-. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Gpx1tm1Ysh allele
023919   B6.129(Cg)-Gpx1tm1Ysh/MgoldJ
View Strains carrying   Gpx1tm1Ysh     (1 strain)

Strains carrying   Park2tm1Shn allele
006582   B6.129S4-Park2tm1Shn/J
View Strains carrying   Park2tm1Shn     (1 strain)

Strains carrying   Park7tm1Shn allele
006577   B6.Cg-Park7tm1Shn/J
View Strains carrying   Park7tm1Shn     (1 strain)

Strains carrying other alleles of Park2
007587   129S-Park2tm1Rpa/J
View Strains carrying other alleles of Park2     (1 strain)

Strains carrying other alleles of Park7
012835   B6;129X1-Park7tm1Cai/Mmjax
View Strains carrying other alleles of Park7     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Glutathione Peroxidase Deficiency; GPXD   (GPX1)
Leprosy, Susceptibility to, 2; LPRS2   (PARK2)
Lung Cancer   (PARK2)
Ovarian Cancer   (PARK2)
Parkinson Disease 2, Autosomal Recessive Juvenile; PARK2   (PARK2)
Parkinson Disease 7, Autosomal Recessive Early-Onset; PARK7   (PARK7)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Gpx1tm1Ysh/Gpx1tm1Ysh Park2tm1Shn/Park2tm1Shn Park7tm1Shn/Park7tm1Shn

        B6.Cg-Park7tm1Shn Gpx1tm1Ysh Park2tm1Shn
  • behavior/neurological phenotype
  • impaired coordination
    • increased latency to fall (rotarod test) observed at 12 and 18 months of age as compared to controls   (MGI Ref ID J:202221)
  • homeostasis/metabolism phenotype
  • increased dopamine level
    • striatal dopamine levels are significantly elevated at 6, 12 and 18 months of age, however, dopamine turnover is similar to controls   (MGI Ref ID J:202221)
  • increased serotonin level
    • striatal serotonin levels are increased at 12 months of age, however, serotonin turnover is similar to controls   (MGI Ref ID J:202221)
  • nervous system phenotype
  • increased dopamine level
    • striatal dopamine levels are significantly elevated at 6, 12 and 18 months of age, however, dopamine turnover is similar to controls   (MGI Ref ID J:202221)
View Research Applications

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

Neurobiology Research
Parkinson's Disease

Research Tools
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Gpx1tm1Ysh
Allele Name targeted mutation 1, Ye-Shih Ho
Allele Type Targeted (knock-out)
Common Name(s) GPX1 KO; GSHPx-1-deficient; GpX-1 KO; Gpx1-;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Gpx1, glutathione peroxidase 1
Chromosome 9
Gene Common Name(s) AI195024; AL033363; CGPx; GPXD; GPx-1; GSHPX1; GSHPx; GSHPx-1; Gpx; cellular GPx; expressed sequence AI195024; expressed sequence AL033363; glutathione peroxidase;
General Note Phenotypic Similarity to Human Syndrome: Inflammatory Bowel Disease (J:71506) as heterozygote or homozygote on a Gpx2tm2Coh homozygote background.
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. [MGI Ref ID J:41169]
 
Allele Symbol Park2tm1Shn
Allele Name targeted mutation 1, Jie Shen
Allele Type Targeted (knock-out)
Common Name(s) parkin -;
Mutation Made By Jie Shen,   Harvard Med Sch/Brigham Women's Hosp
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Park2, Parkinson disease (autosomal recessive, juvenile) 2, parkin
Chromosome 17
Gene Common Name(s) AR-JP; LPRS2; PDJ; PRKN; Park;
Molecular Note Exon 3 was replaced in-frame by the coding sequence for EGFP followed by a PGK-neomycin cassette. RT-PCR analysis indicated that exon 2 spliced to exon 4 in transcripts thus skipping exon 3 entirely. This results in a frame shift and a premature stop codon in exon 5. Western blot analysis using antibody specific to C-terminal sequences indicated the absence of gene product. [MGI Ref ID J:86377]
 
Allele Symbol Park7tm1Shn
Allele Name targeted mutation 1, Jie Shen
Allele Type Targeted (knock-out)
Common Name(s) DJ-1-;
Mutation Made By Jie Shen,   Harvard Med Sch/Brigham Women's Hosp
Strain of Origin(C57BL/6 x 129)F1
ES Cell Line NameMKV6.5
ES Cell Line Strain(C57BL/6 x 129)F1
Gene Symbol and Name Park7, Parkinson disease (autosomal recessive, early onset) 7
Chromosome 4
Gene Common Name(s) CAP1; DJ-1; DJ1; HEL-S-67p; SP22;
Molecular Note Exon 2 was replaced with a pgk-neo cassette. Western blot failed to detect protein in mutant mice. [MGI Ref ID J:98436]

Genotyping

Genotyping Information

Genotyping Protocols

Gpx1tm1Yshalternate1, Standard PCR
Park2tm1Shn, Melt Curve Analysis
Park7tm1Shn, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hennis MR; Marvin MA; Taylor CM 2nd; Goldberg MS. 2013. Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease. Neurobiol Dis 62C:113-123. [PubMed: 24075852]  [MGI Ref ID J:202221]

Additional References

Gpx1tm1Ysh related

Beck MA; Esworthy RS; Ho YS; Chu FF. 1998. Glutathione peroxidase protects mice from viral-induced myocarditis. FASEB J 12(12):1143-9. [PubMed: 9737717]  [MGI Ref ID J:82372]

Chan AW; Ho YS; Chung SK; Chung SS. 2008. Synergistic effect of osmotic and oxidative stress in slow-developing cataract formation. Exp Eye Res 87(5):454-61. [PubMed: 18760274]  [MGI Ref ID J:142446]

Cheng F; Torzewski M; Degreif A; Rossmann H; Canisius A; Lackner KJ. 2013. Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis. PLoS One 8(8):e72063. [PubMed: 23991041]  [MGI Ref ID J:204544]

Cheng W; Fu YX; Porres JM; Ross DA; Lei XG. 1999. Selenium-dependent cellular glutathione peroxidase protects mice against a pro-oxidant-induced oxidation of NADPH, NADH, lipids, and protein. FASEB J 13(11):1467-75. [PubMed: 10428770]  [MGI Ref ID J:56648]

Cheng WH; Quimby FW; Lei XG. 2003. Impacts of glutathione peroxidase-1 knockout on the protection by injected selenium against the pro-oxidant-induced liver aponecrosis and signaling in selenium-deficient mice. Free Radic Biol Med 34(7):918-27. [PubMed: 12654481]  [MGI Ref ID J:118014]

Chu FF; Esworthy RS; Chu PG; Longmate JA; Huycke MM; Wilczynski S; Doroshow JH. 2004. Bacteria-Induced Intestinal Cancer in Mice with Disrupted Gpx1 and Gpx2 Genes. Cancer Res 64(3):962-968. [PubMed: 14871826]  [MGI Ref ID J:88070]

Dayal S; Brown KL; Weydert CJ; Oberley LW; Arning E; Bottiglieri T; Faraci FM; Lentz SR. 2002. Deficiency of glutathione peroxidase-1 sensitizes hyperhomocysteinemic mice to endothelial dysfunction. Arterioscler Thromb Vasc Biol 22(12):1996-2002. [PubMed: 12482825]  [MGI Ref ID J:103367]

Demchenko IT; Atochin DN; Gutsaeva DR; Godfrey RR; Huang PL; Piantadosi CA; Allen BW. 2008. Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects. Am J Physiol Lung Cell Mol Physiol 294(5):L984-90. [PubMed: 18326824]  [MGI Ref ID J:136632]

Esworthy RS; Aranda R; Martin MG; Doroshow JH; Binder SW; Chu FF. 2001. Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. Am J Physiol Gastrointest Liver Physiol 281(3):G848-55. [PubMed: 11518697]  [MGI Ref ID J:71506]

Esworthy RS; Binder SW; Doroshow JH; Chu FF. 2003. Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression. Biol Chem 384(4):597-607. [PubMed: 12751789]  [MGI Ref ID J:103116]

Esworthy RS; Ho YS; Chu FF. 1997. The Gpx1 gene encodes mitochondrial glutathione peroxidase in the mouse liver. Arch Biochem Biophys 340(1):59-63. [PubMed: 9126277]  [MGI Ref ID J:39714]

Esworthy RS; Kim BW; Larson GP; Yip ML; Smith DD; Li M; Chu FF. 2011. Colitis locus on chromosome 2 impacting the severity of early-onset disease in mice deficient in GPX1 and GPX2. Inflamm Bowel Dis 17(6):1373-86. [PubMed: 20872835]  [MGI Ref ID J:171572]

Esworthy RS; Kim BW; Rivas GE; Leto TL; Doroshow JH; Chu FF. 2012. Analysis of candidate colitis genes in the Gdac1 locus of mice deficient in glutathione peroxidase-1 and -2. PLoS One 7(9):e44262. [PubMed: 22970191]  [MGI Ref ID J:191887]

Esworthy RS; Mann JR; Sam M; Chu FF. 2000. Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from gamma-irradiation damage. Am J Physiol Gastrointest Liver Physiol 279(2):G426-36. [PubMed: 10915653]  [MGI Ref ID J:63988]

Esworthy RS; Yang L; Frankel PH; Chu FF. 2005. Epithelium-specific glutathione peroxidase, gpx2, is involved in the prevention of intestinal inflammation in selenium-deficient mice. J Nutr 135(4):740-5. [PubMed: 15795427]  [MGI Ref ID J:97545]

Forgione MA; Cap A; Liao R; Moldovan NI; Eberhardt RT; Lim CC; Jones J; Goldschmidt-Clermont PJ; Loscalzo J. 2002. Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure Circulation 106(9):1154-1158. [PubMed: 12196344]  [MGI Ref ID J:111478]

Forgione MA; Weiss N; Heydrick S; Cap A; Klings ES; Bierl C; Eberhardt RT; Farber HW; Loscalzo J. 2002. Cellular glutathione peroxidase deficiency and endothelial dysfunction. Am J Physiol Heart Circ Physiol 282(4):H1255-61. [PubMed: 11893559]  [MGI Ref ID J:75857]

Fu Y; Cheng WH; Porres JM; Ross DA; Lei XG. 1999. Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquat-induced oxidative stress. Free Radic Biol Med 27(5-6):605-11. [PubMed: 10490281]  [MGI Ref ID J:59488]

Galasso G; Schiekofer S; Sato K; Shibata R; Handy DE; Ouchi N; Leopold JA; Loscalzo J; Walsh K. 2006. Impaired angiogenesis in glutathione peroxidase-1-deficient mice is associated with endothelial progenitor cell dysfunction. Circ Res 98(2):254-61. [PubMed: 16373599]  [MGI Ref ID J:118088]

Gao J; Xiong Y; Ho YS; Liu X; Chua CC; Xu X; Wang H; Hamdy R; Chua BH. 2008. Glutathione peroxidase 1-deficient mice are more susceptible to doxorubicin-induced cardiotoxicity. Biochim Biophys Acta 1783(10):2020-9. [PubMed: 18602426]  [MGI Ref ID J:140888]

Hahn MA; Hahn T; Lee DH; Esworthy RS; Kim BW; Riggs AD; Chu FF; Pfeifer GP. 2008. Methylation of polycomb target genes in intestinal cancer is mediated by inflammation. Cancer Res 68(24):10280-9. [PubMed: 19074896]  [MGI Ref ID J:142237]

Han C; Someya S. 2013. Mouse models of age-related mitochondrial neurosensory hearing loss. Mol Cell Neurosci 55:95-100. [PubMed: 22820179]  [MGI Ref ID J:203587]

Han ES; Muller FL; Perez VI; Qi W; Liang H; Xi L; Fu C; Doyle E; Hickey M; Cornell J; Epstein CJ; Roberts LJ; Van Remmen H; Richardson A. 2008. The in vivo gene expression signature of oxidative stress. Physiol Genomics 34(1):112-26. [PubMed: 18445702]  [MGI Ref ID J:145302]

Hill KE; Wu S; Motley AK; Stevenson TD; Winfrey VP; Capecchi MR; Atkins JF; Burk RF. 2012. Production of selenoprotein P (Sepp1) by hepatocytes is central to selenium homeostasis. J Biol Chem 287(48):40414-24. [PubMed: 23038251]  [MGI Ref ID J:192636]

Ho YS; Magnenat JL; Bronson RT; Cao J; Gargano M; Sugawara M ; Funk CD. 1997. Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 272(26):16644-51. [PubMed: 9195979]  [MGI Ref ID J:41169]

Jiang D; Akopian G; Ho YS; Walsh JP; Andersen JK. 2000. Chronic brain oxidation in a glutathione peroxidase knockout mouse model results in increased resistance to induced epileptic seizures. Exp Neurol 164(2):257-68. [PubMed: 10915565]  [MGI Ref ID J:115327]

Johnson RM; Goyette G Jr; Ravindranath Y; Ho YS. 2005. Hemoglobin autoxidation and regulation of endogenous H(2)O(2) levels in erythrocytes. Free Radic Biol Med 39(11):1407-17. [PubMed: 16274876]  [MGI Ref ID J:102737]

Johnson RM; Goyette G; Ravindranath Y; Ho YS. 2000. Red cells from glutathione peroxidase-1-deficient mice have nearly normal defenses against exogenous peroxides Blood 96(5):1985-8. [PubMed: 10961904]  [MGI Ref ID J:64216]

Johnson RM; Ho YS; Yu DY; Kuypers FA; Ravindranath Y; Goyette GW. 2010. The effects of disruption of genes for peroxiredoxin-2, glutathione peroxidase-1, and catalase on erythrocyte oxidative metabolism. Free Radic Biol Med 48(4):519-525. [PubMed: 19969073]  [MGI Ref ID J:156771]

Keller JN; Huang FF; Zhu H; Yu J; Ho YS; Kindy TS. 2000. Oxidative stress-associated impairment of proteasome activity during ischemia-reperfusion injury. J Cereb Blood Flow Metab 20(10):1467-73. [PubMed: 11043909]  [MGI Ref ID J:133829]

Kim BW; Esworthy RS; Hahn MA; Pfeifer GP; Chu FF. 2012. Expression of lactoperoxidase in differentiated mouse colon epithelial cells. Free Radic Biol Med 52(9):1569-76. [PubMed: 22343415]  [MGI Ref ID J:183260]

Klivenyi P; Andreassen OA; Ferrante RJ; Dedeoglu A; Mueller G; Lancelot E; Bogdanov M; Andersen JK; Jiang D; Beal MF. 2000. Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. J Neurosci 20(1):1-7. [PubMed: 10627575]  [MGI Ref ID J:59142]

Lee DH; Esworthy RS; Chu C; Pfeifer GP; Chu FF. 2006. Mutation accumulation in the intestine and colon of mice deficient in two intracellular glutathione peroxidases. Cancer Res 66(20):9845-51. [PubMed: 17047045]  [MGI Ref ID J:114994]

Lee S; Shin HS; Shireman PK; Vasilaki A; Van Remmen H; Csete ME. 2006. Glutathione-peroxidase-1 null muscle progenitor cells are globally defective. Free Radic Biol Med 41(7):1174-84. [PubMed: 16962942]  [MGI Ref ID J:112583]

Lei XG; Zhu JH; McClung JP; Aregullin M; Roneker CA. 2006. Mice deficient in Cu,Zn-superoxide dismutase are resistant to acetaminophen toxicity. Biochem J 399(3):455-61. [PubMed: 16831125]  [MGI Ref ID J:116036]

Lim CC; Bryan NS; Jain M; Garcia-Saura MF; Fernandez BO; Sawyer DB; Handy DE; Loscalzo J; Feelisch M; Liao R. 2009. Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms. Am J Physiol Heart Circ Physiol 297(6):H2144-53. [PubMed: 19801492]  [MGI Ref ID J:158230]

Liu G; Feinstein SI; Wang Y; Dodia C; Fisher D; Yu K; Ho YS; Fisher AB. 2010. Comparison of glutathione peroxidase 1 and peroxiredoxin 6 in protection against oxidative stress in the mouse lung. Free Radic Biol Med 49(7):1172-81. [PubMed: 20627125]  [MGI Ref ID J:164603]

Lubos E; Mahoney CE; Leopold JA; Zhang YY; Loscalzo J; Handy DE. 2010. Glutathione peroxidase-1 modulates lipopolysaccharide-induced adhesion molecule expression in endothelial cells by altering CD14 expression. FASEB J 24(7):2525-32. [PubMed: 20219985]  [MGI Ref ID J:162352]

Muller FL; Lustgarten MS; Jang Y; Richardson A; Van Remmen H. 2007. Trends in oxidative aging theories. Free Radic Biol Med 43(4):477-503. [PubMed: 17640558]  [MGI Ref ID J:123504]

Ohlemiller KK; McFadden SL; Ding DL; Lear PM; Ho YS. 2000. Targeted mutation of the gene for cellular glutathione peroxidase (Gpx1) increases noise-induced hearing loss in mice. J Assoc Res Otolaryngol 1(3):243-54. [PubMed: 11545230]  [MGI Ref ID J:113167]

Olson GE; Whitin JC; Hill KE; Winfrey VP; Motley AK; Austin LM; Deal J; Cohen HJ; Burk RF. 2009. EXTRACELLULAR GLUTATHIONE PEROXIDASE (Gpx3) BINDS SPECIFICALLY TO BASEMENT MEMBRANES OF MOUSE RENAL CORTEX TUBULE CELLS. Am J Physiol Renal Physiol :. [PubMed: 20015939]  [MGI Ref ID J:159745]

Rathore R; Zheng YM; Niu CF; Liu QH; Korde A; Ho YS; Wang YX. 2008. Hypoxia activates NADPH oxidase to increase [ROS]i and [Ca2+]i through the mitochondrial ROS-PKCepsilon signaling axis in pulmonary artery smooth muscle cells. Free Radic Biol Med 45(9):1223-31. [PubMed: 18638544]  [MGI Ref ID J:141206]

Reddy VN; Giblin FJ; Lin LR; Dang L; Unakar NJ; Musch DC; Boyle DL; Takemoto LJ; Ho YS; Knoernschild T; Juenemann A; Lutjen-Drecoll E. 2001. Glutathione peroxidase-1 deficiency leads to increased nuclear light scattering, membrane damage, and cataract formation in gene-knockout mice. Invest Ophthalmol Vis Sci 42(13):3247-55. [PubMed: 11726630]  [MGI Ref ID J:108431]

South PK; Levander OA; Smith AD. 2002. Effects of dietary iron overload on glutathione peroxidase knockout mice. Biol Trace Elem Res 88(1):79-85. [PubMed: 12117267]  [MGI Ref ID J:113070]

Spector A; Kuszak JR; Ma W; Wang RR. 2001. The effect of aging on glutathione peroxidase-i knockout mice-resistance of the lens to oxidative stress. Exp Eye Res 72(5):533-45. [PubMed: 11311045]  [MGI Ref ID J:69125]

Spector A; Kuszak JR; Ma W; Wang RR; Ho Y; Yang Y. 1998. The effect of photochemical stress upon the lenses of normal and glutathione peroxidase-1 knockout mice. Exp Eye Res 67(4):457-71. [PubMed: 9820794]  [MGI Ref ID J:106611]

Spector A; Yang Y; Ho YS; Magnenat JL; Wang RR; Ma W; Li WC. 1996. Variation in cellular glutathione peroxidase activity in lens epithelial cells, transgenics and knockouts does not significantly change the response to H2O2 stress. Exp Eye Res 62(5):521-40. [PubMed: 8759521]  [MGI Ref ID J:110762]

Torzewski M; Ochsenhirt V; Kleschyov AL; Oelze M; Daiber A; Li H; Rossmann H; Tsimikas S; Reifenberg K; Cheng F; Lehr HA; Blankenberg S; Forstermann U; Munzel T; Lackner KJ. 2007. Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27(4):850-7. [PubMed: 17255533]  [MGI Ref ID J:135067]

Van Remmen H; Qi W; Sabia M; Freeman G; Estlack L; Yang H; Mao Guo Z; Huang TT; Strong R; Lee S; Epstein CJ; Richardson A. 2004. Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress. Free Radic Biol Med 36(12):1625-34. [PubMed: 15182862]  [MGI Ref ID J:90710]

Vasilaki A; Csete M; Pye D; Lee S; Palomero J; McArdle F; Van Remmen H; Richardson A; McArdle A; Faulkner JA; Jackson MJ. 2006. Genetic modification of the manganese superoxide dismutase/glutathione peroxidase 1 pathway influences intracellular ROS generation in quiescent, but not contracting, skeletal muscle cells. Free Radic Biol Med 41(11):1719-25. [PubMed: 17145560]  [MGI Ref ID J:116698]

Walshe J; Serewko-Auret MM; Teakle N; Cameron S; Minto K; Smith L; Burcham PC; Russell T; Strutton G; Griffin A; Chu FF; Esworthy S; Reeve V; Saunders NA. 2007. Inactivation of glutathione peroxidase activity contributes to UV-induced squamous cell carcinoma formation. Cancer Res 67(10):4751-8. [PubMed: 17510403]  [MGI Ref ID J:121730]

Wang L; Jiang Z; Lei XG. 2012. Knockout of SOD1 alters murine hepatic glycolysis, gluconeogenesis, and lipogenesis. Free Radic Biol Med 53(9):1689-96. [PubMed: 22974764]  [MGI Ref ID J:190130]

Wolf N; Penn P; Pendergrass W; Van Remmen H; Bartke A; Rabinovitch P; Martin GM. 2005. Age-related cataract progression in five mouse models for anti-oxidant protection or hormonal influence. Exp Eye Res 81(3):276-85. [PubMed: 16129095]  [MGI Ref ID J:136934]

Yoshida T; Maulik N; Engelman RM; Ho YS; Magnenat JL; Rousou JA; Flack JE 3rd; Deaton D; Das DK. 1997. Glutathione peroxidase knockout mice are susceptible to myocardial ischemia reperfusion injury. Circulation 96(9 Suppl):II-216-20. [PubMed: 9386101]  [MGI Ref ID J:44499]

Zhu JH; Lei XG. 2006. Double null of selenium-glutathione peroxidase-1 and copper, zinc-superoxide dismutase enhances resistance of mouse primary hepatocytes to acetaminophen toxicity. Exp Biol Med (Maywood) 231(5):545-52. [PubMed: 16636302]  [MGI Ref ID J:135749]

Zhu JH; Lei XG. 2011. Lipopolysaccharide-induced hepatic oxidative injury is not potentiated by knockout of GPX1 and SOD1 in mice. Biochem Biophys Res Commun 404(1):559-63. [PubMed: 21145306]  [MGI Ref ID J:167441]

Zhu JH; Zhang X; McClung JP; Lei XG. 2006. Impact of Cu, Zn-superoxide dismutase and Se-dependent glutathione peroxidase-1 knockouts on acetaminophen-induced cell death and related signaling in murine liver. Exp Biol Med (Maywood) 231(11):1726-32. [PubMed: 17138759]  [MGI Ref ID J:135914]

Park2tm1Shn related

Berthet A; Bezard E; Porras G; Fasano S; Barroso-Chinea P; Dehay B; Martinez A; Thiolat ML; Nosten-Bertrand M; Giros B; Baufreton J; Li Q; Bloch B; Martin-Negrier ML. 2012. L-DOPA Impairs Proteasome Activity in Parkinsonism through D1 Dopamine Receptor. J Neurosci 32(2):681-91. [PubMed: 22238104]  [MGI Ref ID J:179902]

Chen Y; Sawada O; Kohno H; Le YZ; Subauste C; Maeda T; Maeda A. 2013. Autophagy protects the retina from light-induced degeneration. J Biol Chem 288(11):7506-18. [PubMed: 23341467]  [MGI Ref ID J:196891]

Ekholm-Reed S; Goldberg MS; Schlossmacher MG; Reed SI. 2013. Parkin-dependent degradation of the F-box protein Fbw7beta promotes neuronal survival in response to oxidative stress by stabilizing Mcl-1. Mol Cell Biol 33(18):3627-43. [PubMed: 23858059]  [MGI Ref ID J:204747]

Frank-Cannon TC; Tran T; Ruhn KA; Martinez TN; Hong J; Marvin M; Hartley M; Trevino I; O'Brien DE; Casey B; Goldberg MS; Tansey MG. 2008. Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J Neurosci 28(43):10825-34. [PubMed: 18945890]  [MGI Ref ID J:140159]

Goldberg MS; Fleming SM; Palacino JJ; Cepeda C; Lam HA; Bhatnagar A; Meloni EG; Wu N; Ackerson LC; Klapstein GJ; Gajendiran M; Roth BL; Chesselet MF; Maidment NT; Levine MS; Shen J. 2003. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278(44):43628-35. [PubMed: 12930822]  [MGI Ref ID J:86377]

Hoshino A; Ariyoshi M; Okawa Y; Kaimoto S; Uchihashi M; Fukai K; Iwai-Kanai E; Ikeda K; Ueyama T; Ogata T; Matoba S. 2014. Inhibition of p53 preserves Parkin-mediated mitophagy and pancreatic beta-cell function in diabetes. Proc Natl Acad Sci U S A 111(8):3116-21. [PubMed: 24516131]  [MGI Ref ID J:206823]

Kao SY. 2009. Regulation of DNA repair by parkin. Biochem Biophys Res Commun 382(2):321-5. [PubMed: 19285961]  [MGI Ref ID J:147872]

Kim KY; Stevens MV; Akter MH; Rusk SE; Huang RJ; Cohen A; Noguchi A; Springer D; Bocharov AV; Eggerman TL; Suen DF; Youle RJ; Amar M; Remaley AT; Sack MN. 2011. Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells. J Clin Invest 121(9):3701-12. [PubMed: 21865652]  [MGI Ref ID J:178238]

Kitada T; Pisani A; Karouani M; Haburcak M; Martella G; Tscherter A; Platania P; Wu B; Pothos EN; Shen J. 2009. Impaired dopamine release and synaptic plasticity in the striatum of parkin-/- mice. J Neurochem 110(2):613-21. [PubMed: 19457102]  [MGI Ref ID J:150857]

Kubli DA; Zhang X; Lee Y; Hanna RA; Quinsay MN; Nguyen CK; Jimenez R; Petrosyan S; Murphy AN; Gustafsson AB. 2013. Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem 288(2):915-26. [PubMed: 23152496]  [MGI Ref ID J:193741]

Lee Y; Lee HY; Hanna RA; Gustafsson AB. 2011. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol 301(5):H1924-31. [PubMed: 21890690]  [MGI Ref ID J:178330]

Madeo G; Martella G; Schirinzi T; Ponterio G; Shen J; Bonsi P; Pisani A. 2012. Aberrant striatal synaptic plasticity in monogenic parkinsonisms. Neuroscience 211:126-35. [PubMed: 21839811]  [MGI Ref ID J:184659]

Martella G; Platania P; Vita D; Sciamanna G; Cuomo D; Tassone A; Tscherter A; Kitada T; Bonsi P; Shen J; Pisani A. 2009. Enhanced sensitivity to group II mGlu receptor activation at corticostriatal synapses in mice lacking the familial parkinsonism-linked genes PINK1 or Parkin. Exp Neurol 215(2):388-96. [PubMed: 19071114]  [MGI Ref ID J:144364]

Palacino JJ; Sagi D; Goldberg MS; Krauss S; Motz C; Wacker M; Klose J; Shen J. 2004. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279(18):18614-22. [PubMed: 14985362]  [MGI Ref ID J:89508]

Pickrell AM; Pinto M; Moraes CT. 2013. Mouse models of Parkinson's disease associated with mitochondrial dysfunction. Mol Cell Neurosci 55:87-94. [PubMed: 22954895]  [MGI Ref ID J:203680]

Rosen KM; Veereshwarayya V; Moussa CE; Fu Q; Goldberg MS; Schlossmacher MG; Shen J; Querfurth HW. 2006. Parkin protects against mitochondrial toxins and beta-amyloid accumulation in skeletal muscle cells. J Biol Chem 281(18):12809-16. [PubMed: 16517603]  [MGI Ref ID J:112711]

Sul JW; Park MY; Shin J; Kim YR; Yoo SE; Kong YY; Kwon KS; Lee YH; Kim E. 2013. Accumulation of the parkin substrate, FAF1, plays a key role in the dopaminergic neurodegeneration. Hum Mol Genet 22(8):1558-73. [PubMed: 23307929]  [MGI Ref ID J:194987]

Zhang C; Lin M; Wu R; Wang X; Yang B; Levine AJ; Hu W; Feng Z. 2011. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci U S A 108(39):16259-64. [PubMed: 21930938]  [MGI Ref ID J:177137]

Park7tm1Shn related

Aleyasin H; Rousseaux MW; Marcogliese PC; Hewitt SJ; Irrcher I; Joselin AP; Parsanejad M; Kim RH; Rizzu P; Callaghan SM; Slack RS; Mak TW; Park DS. 2010. DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway. Proc Natl Acad Sci U S A 107(7):3186-91. [PubMed: 20133695]  [MGI Ref ID J:157558]

Aron L; Klein P; Pham TT; Kramer ER; Wurst W; Klein R. 2010. Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS Biol 8(4):e1000349. [PubMed: 20386724]  [MGI Ref ID J:159857]

Giaime E; Yamaguchi H; Gautier CA; Kitada T; Shen J. 2012. Loss of DJ-1 does not affect mitochondrial respiration but increases ROS production and mitochondrial permeability transition pore opening. PLoS One 7(7):e40501. [PubMed: 22792356]  [MGI Ref ID J:189646]

Goldberg MS; Pisani A; Haburcak M; Vortherms TA; Kitada T; Costa C; Tong Y; Martella G; Tscherter A; Martins A; Bernardi G; Roth BL; Pothos EN; Calabresi P; Shen J. 2005. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45(4):489-96. [PubMed: 15721235]  [MGI Ref ID J:98436]

Kim YC; Kitaura H; Iguchi-Ariga SM; Ariga H. 2010. DJ-1, an oncogene and causative gene for familial Parkinson's disease, is essential for SV40 transformation in mouse fibroblasts through up-regulation of c-Myc. FEBS Lett 584(18):3891-5. [PubMed: 20708612]  [MGI Ref ID J:164395]

Madeo G; Martella G; Schirinzi T; Ponterio G; Shen J; Bonsi P; Pisani A. 2012. Aberrant striatal synaptic plasticity in monogenic parkinsonisms. Neuroscience 211:126-35. [PubMed: 21839811]  [MGI Ref ID J:184659]

Martella G; Madeo G; Schirinzi T; Tassone A; Sciamanna G; Spadoni F; Stefani A; Shen J; Pisani A; Bonsi P. 2011. Altered profile and D2-dopamine receptor modulation of high voltage-activated calcium current in striatal medium spiny neurons from animal models of Parkinson's disease. Neuroscience 177:240-51. [PubMed: 21195752]  [MGI Ref ID J:170553]

Pisani A; Martella G; Tscherter A; Costa C; Mercuri NB; Bernardi G; Shen J; Calabresi P. 2006. Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase. Neurobiol Dis 23(1):54-60. [PubMed: 16624565]  [MGI Ref ID J:111114]

Sheng C; Heng X; Zhang G; Xiong R; Li H; Zhang S; Chen S. 2013. DJ-1 deficiency perturbs microtubule dynamics and impairs striatal neurite outgrowth. Neurobiol Aging 34(2):489-98. [PubMed: 22609282]  [MGI Ref ID J:194438]

Shtifman A; Zhong N; Lopez JR; Shen J; Xu J. 2011. Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. Neurobiol Aging 32(1):125-32. [PubMed: 19683835]  [MGI Ref ID J:168285]

Usami Y; Hatano T; Imai S; Kubo S; Sato S; Saiki S; Fujioka Y; Ohba Y; Sato F; Funayama M; Eguchi H; Shiba K; Ariga H; Shen J; Hattori N. 2011. DJ-1 associates with synaptic membranes. Neurobiol Dis 43(3):651-62. [PubMed: 21645620]  [MGI Ref ID J:176995]

Yamaguchi H; Shen J. 2007. Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice. Mol Neurodegener 2:10. [PubMed: 17535435]  [MGI Ref ID J:134518]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as homozygotes for each targeted mutation.
Mating SystemFemale Homozygous for Park7tm1Shn, Homozygous for Gpx1tm1Ysh, Homozygous for Park2tm1Shn x Male Homozygous for Park7tm1Shn, Homozygous for Gpx1tm1Ysh, Homozygous for Park2tm1Shn

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 23-MAR-15

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHomozygous for Park7tm1Shn, Homozygous for Gpx1tm1Ysh, Homozygous for Park2tm1Shn  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Park7tm1Shn, Homozygous for Gpx1tm1Ysh, Homozygous for Park2tm1Shn  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

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.
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JAX® Mice
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Tel: 1-800-422-6423 or 1-207-288-5845
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Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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Contact information

General inquiries regarding Terms of Use

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phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

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The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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