Strain Name:

B6.129X1-Nfe2l2tm1Ywk/J

Stock Number:

017009

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Availability:

Repository- Live

These Nfe2l2tm1Ywk (NRF2) knockout mice may be useful for studying oxidative stress in the pathogenesis of age-related macular degeneration, diabetes, Parkinson's disease, and other inflammatory degenerative diseases as well as studies of cancer, multiple sclerosis, liver cirrhosis, atherosclerosis, injury and wound healing, and more.

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 SystemHomozygote x Heterozygote         (Female x Male)   04-MAR-13
Mating SystemHeterozygote x Homozygote         (Female x Male)   04-MAR-13
Specieslaboratory mouse
GenerationN10pN1+F3 (17-DEC-13)
Generation Definitions
 
Donating Investigator Michael L. Freeman,   Vanderbilt University

Appearance
Black or Agouti*
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Description
In this NRF2 knockout strain, a β-galactosidase (lacZ) reporter followed by a neomycin resistance (neo) cassette replaces exon 5 and part of exon 4 encoding the nuclear factor, erythroid derived 2, like 2 gene (Nfe2l2) gene, abolishing gene function. Homozygotes are viable, fertile, and normal in size. NRF2, a member of the "cap 'n' collar" (CNC) subfamily of the basic region-leucine zipper transcription factors, is a regulator of endogenous antioxidant protection, microglial function, and chronic neuroinflammation. Inactivation of the CNC, DNA binding, and leucine zipper domains in Nrf2-/- mice results in age-related macular degeneration (AMD)-like retinal pathology, spontaneous choroidal neovascularization (CNV), increased sensitivity to toxins, impaired adipogenesis, abnormal mitochondria, and an increase in proinflammatory gene expression in microglia and astrocytes. The donating investigator reports that lacZ failed to generate any detectable b-galactosidase activity.

Development
A targeting vector was designed to replace exon 5 and part of exon 4 encoding the nuclear factor, erythroid derived 2, like 2 (Nfe2l2) gene with a β-galactosidase (lacZ) reporter followed by a neomycin resistance (neo) cassette and a polyadenylation sequence. The construct was electroporated into 129X1/SvJ-derived JM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6 mice to generate a colony of Nrf2-/- mice. The donating investigator reported that these mice were backcrossed to C57BL/6J (see SNP note below) for at least 10 generations . Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While 1 of the 27 markers throughout the genome was segregating for 129, suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

  Control
   Heterozygote from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

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View Parkinson's Disease Models     (112 strains)

Additional Web Information

Fluorescent Proteins/lacZ Systems

Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Nfe2l2tm1Ywk/Nfe2l2tm1Ywk

        involves: 129X1/SvJ
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype
    • at 6 weeks of age, all hematological indices are within normal ranges   (MGI Ref ID J:37053)
    • abnormal erythrocyte physiology
      • erythrocytes exhibit increased sensitivity to hydrogen peroxide-induced cytotoxicity compared to similarly treated wild-type cell   (MGI Ref ID J:91407)
      • erythrocytes exhibit increased methemoglobin formation after incubation with high concentration of hydrogen peroxide unlike similarly treated wild-type cells   (MGI Ref ID J:91407)
      • erythrocytes exhibit increased levels of IgG and IgM due to increased levels of oxidative damage compared to wild-type cells   (MGI Ref ID J:91407)
      • hydrogen peroxide-treated erythrocytes exhibit increased IgG binding compared to similarly treated wild-type cells   (MGI Ref ID J:91407)
    • abnormal splenocyte physiology
      • splenocytes exhibit increased sensitivity to hydrogen peroxide-induced cytotoxicity compared to wild-type cells   (MGI Ref ID J:91407)
      • increased splenocyte apoptosis   (MGI Ref ID J:91407)
    • acanthocytosis   (MGI Ref ID J:91407)
    • anisocytosis
      • mild at 6 months of age   (MGI Ref ID J:91407)
    • decreased erythrocyte cell number   (MGI Ref ID J:91407)
    • decreased hematocrit   (MGI Ref ID J:91407)
    • decreased hemoglobin content   (MGI Ref ID J:91407)
    • decreased platelet cell number   (MGI Ref ID J:91407)
    • enlarged spleen   (MGI Ref ID J:91407)
      • increased spleen weight
    • hemolytic anemia
      • mice exhibit hemolytic anemia at 6 months that is more severe in older mice   (MGI Ref ID J:91407)
    • increased macrophage cell number
      • at day 13 post-wound unlike in wild-type mice   (MGI Ref ID J:100106)
    • increased number of Howell-Jolly bodies   (MGI Ref ID J:91407)
    • poikilocytosis
      • mild at 6 months of age   (MGI Ref ID J:91407)
      • schistocytosis   (MGI Ref ID J:91407)
    • reticulocytosis
      • due to increased production   (MGI Ref ID J:91407)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • the rate of wound is normal   (MGI Ref ID J:100106)
    • decreased circulating interleukin-1 beta level
      • by 30% in mice with 1 day old wounds compared to similarly treated wild-type mice   (MGI Ref ID J:100106)
    • increased circulating bilirubin level   (MGI Ref ID J:130473)
    • increased circulating interleukin-1 beta level
      • by 60% in mice with 5 day old wounds compared to similarly treated wild-type mice   (MGI Ref ID J:100106)
      • at day 13 post-wound, mice exhibit a 4-fold higher level of plasma IL-1b compared to similarly treated wild-type mice   (MGI Ref ID J:100106)
    • increased lactate dehydrogenase level
      • following incubation of erythrocytes in hydrogen peroxide   (MGI Ref ID J:91407)
  • cellular phenotype
  • decreased hepatocyte proliferation
    • during regeneration following partial hepatectomy   (MGI Ref ID J:130473)
  • increased apoptosis
    • primary fibroblasts exhibit a small increase in apoptosis compared to wild-type cells   (MGI Ref ID J:86725)
    • increased splenocyte apoptosis   (MGI Ref ID J:91407)
  • increased cellular sensitivity to hydrogen peroxide
    • in splenocytes and erythrocytes   (MGI Ref ID J:91407)
  • oxidative stress
    • cultured fibroblasts exhibit a 2-fold increase in oxidative stress compared to wild-type cells   (MGI Ref ID J:86725)
    • hydrogen peroxide-treated erythrocytes exhibit increased IgG binding compared to similarly treated wild-type cells   (MGI Ref ID J:91407)
    • myelin sheaths accumulate evidence of oxidant injury unlike in wild-type mice   (MGI Ref ID J:122195)
    • oxidative stress in primary hepatocytes is increased compared to in wild-type cells   (MGI Ref ID J:130473)
  • nervous system phenotype
  • abnormal myelin sheath morphology
    • mice exhibit multiloculated cystic dilation and whorls of myelin unlike wild-type mice   (MGI Ref ID J:122195)
    • myelin sheaths accumulate evidence of oxidant injury unlike in wild-type mice   (MGI Ref ID J:122195)
  • astrocytosis
    • in the absence of neurodegeneration   (MGI Ref ID J:122195)
  • spongiform encephalopathy
    • 54% of mice develop vacuolar leukoencephalopathy at a mean age of 8 months wild-type mice   (MGI Ref ID J:122195)
    • by 1 year of age, all mice exhibit vacuolar leukoencephalopathy affecting all areas of the brain and prominently in the cerebellar and pontine white tracts   (MGI Ref ID J:122195)
    • however, neurodegeneration is not observed   (MGI Ref ID J:122195)
  • liver/biliary system phenotype
  • abnormal liver physiology
    • during regeneration following partial hepatectomy, hepatocyte apoptosis rates are increased 5-fold compared to in similarly treated wild-type mice   (MGI Ref ID J:130473)
    • oxidative stress in primary hepatocytes is increased compared to in wild-type cells   (MGI Ref ID J:130473)
    • decreased hepatocyte proliferation
      • during regeneration following partial hepatectomy   (MGI Ref ID J:130473)
    • decreased liver regeneration
  • decreased liver weight   (MGI Ref ID J:130473)
  • craniofacial phenotype
  • abnormal tooth morphology
    • teeth are white unlike in wild-type mice   (MGI Ref ID J:91407)
  • immune system phenotype
  • abnormal spleen physiology
    • spleen inflammation   (MGI Ref ID J:91407)
    • abnormal splenocyte physiology
      • splenocytes exhibit increased sensitivity to hydrogen peroxide-induced cytotoxicity compared to wild-type cells   (MGI Ref ID J:91407)
      • increased splenocyte apoptosis   (MGI Ref ID J:91407)
  • decreased circulating interleukin-1 beta level
    • by 30% in mice with 1 day old wounds compared to similarly treated wild-type mice   (MGI Ref ID J:100106)
  • enlarged spleen   (MGI Ref ID J:91407)
    • increased spleen weight
  • increased circulating interleukin-1 beta level
    • by 60% in mice with 5 day old wounds compared to similarly treated wild-type mice   (MGI Ref ID J:100106)
    • at day 13 post-wound, mice exhibit a 4-fold higher level of plasma IL-1b compared to similarly treated wild-type mice   (MGI Ref ID J:100106)
  • increased macrophage cell number
    • at day 13 post-wound unlike in wild-type mice   (MGI Ref ID J:100106)
  • embryogenesis phenotype
  • *normal* embryogenesis phenotype
    • mice develop normally at E13.5 and E15.5   (MGI Ref ID J:37053)
  • growth/size/body phenotype
  • abnormal tooth morphology
    • teeth are white unlike in wild-type mice   (MGI Ref ID J:91407)

Nfe2l2tm1Ywk/Nfe2l2tm1Ywk

        involves: 129X1/SvJ * C57BL
  • mortality/aging
  • increased sensitivity to xenobiotic induced morbidity/mortality
    • mice treated with 0.5% and 0.1% BHT (BHA and butylated hydroxytoluene) exhibit 59% and 80% mortality, respectively, unlike similarly treated wild-type mice that do not die   (MGI Ref ID J:112943)
  • respiratory system phenotype
  • enlarged lung
    • lungs of BHT-treated mice are enlarged unlike in similarly treated wild-type mice   (MGI Ref ID J:112943)
  • lung hemorrhage
    • lungs of BHT-treated mice are hemorrhagic unlike in similarly treated wild-type mice   (MGI Ref ID J:112943)
  • cardiovascular system phenotype
  • lung hemorrhage
    • lungs of BHT-treated mice are hemorrhagic unlike in similarly treated wild-type mice   (MGI Ref ID J:112943)
  • homeostasis/metabolism phenotype
  • increased physiological sensitivity to xenobiotic
    • mice treated with BHT (BHA and butylated hydroxytoluene) exhibit increased lung injury and mortality compared to similarly treated wild-type mice   (MGI Ref ID J:112943)
    • lungs of BHT-treated mice are enlarged and hemorrhagic with pulmonary infiltrates and destruction of alveolar structure unlike in similarly treated wild-type mice   (MGI Ref ID J:112943)
  • increased sensitivity to xenobiotic induced morbidity/mortality
    • mice treated with 0.5% and 0.1% BHT (BHA and butylated hydroxytoluene) exhibit 59% and 80% mortality, respectively, unlike similarly treated wild-type mice that do not die   (MGI Ref ID J:112943)
View Research Applications

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

Cancer Research
Other

Cardiovascular Research
Atherosclerosis

Diabetes and Obesity Research

Immunology, Inflammation and Autoimmunity Research

Internal/Organ Research
Wound Healing

Neurobiology Research
Parkinson's Disease
      increased vulnerability to MPTP

Research Tools
Toxicology Research
      free radical research

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nfe2l2tm1Ywk
Allele Name targeted mutation 1, Yuet Wai Kan
Allele Type Targeted (Null/Knockout)
Common Name(s) NRF2-; Nrf2 KO;
Mutation Made By Yuet Wai Kan,   University of California SF
Strain of Origin129X1/SvJ
Gene Symbol and Name Nfe2l2, nuclear factor, erythroid derived 2, like 2
Chromosome 2
Gene Common Name(s) AI194320; NRF2; expressed sequence AI194320;
Molecular Note A 4.2 kb segment, includind part of exon 4 and all of exon 5, was replaced by an in-frame lacZ gene followed by a neomycin selection cassette. Northern blot analysis on RNA derived from various tissues confirmed that a fusion transcript was detectable in intestine of homozygous mice, but no wild-type transcript was detectable in any tissue. However, no fusion protein was detected by histochemical staining in any adult tissue. [MGI Ref ID J:37053]

Genotyping

Genotyping Information

Genotyping Protocols

Nfe2l2tm1Ywk, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chan K; Lu R; Chang JC; Kan YW. 1996. NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development. Proc Natl Acad Sci U S A 93(24):13943-8. [PubMed: 8943040]  [MGI Ref ID J:37053]

Additional References

Nfe2l2tm1Ywk related

Al-Sawaf O; Fragoulis A; Rosen C; Kan YW; Sonmez TT; Pufe T; Wruck CJ. 2014. Nrf2 protects against TWEAK-mediated skeletal muscle wasting. Sci Rep 4:3625. [PubMed: 24406502]  [MGI Ref ID J:210102]

Almazari I; Park JM; Park SA; Suh JY; Na HK; Cha YN; Surh YJ. 2012. Guggulsterone induces heme oxygenase-1 expression through activation of Nrf2 in human mammary epithelial cells: PTEN as a putative target. Carcinogenesis 33(2):368-76. [PubMed: 22095074]  [MGI Ref ID J:181025]

Barajas B; Che N; Yin F; Rowshanrad A; Orozco LD; Gong KW; Wang X; Castellani LW; Reue K; Lusis AJ; Araujo JA. 2011. NF-E2-related factor 2 promotes atherosclerosis by effects on plasma lipoproteins and cholesterol transport that overshadow antioxidant protection. Arterioscler Thromb Vasc Biol 31(1):58-66. [PubMed: 20947826]  [MGI Ref ID J:184195]

Beyer TA; Xu W; Teupser D; auf dem Keller U; Bugnon P; Hildt E; Thiery J; Kan YW; Werner S. 2008. Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance. EMBO J 27(1):212-23. [PubMed: 18059474]  [MGI Ref ID J:130473]

Braun S; Hanselmann C; Gassmann MG; auf dem Keller U; Born-Berclaz C; Chan K; Kan YW; Werner S. 2002. Nrf2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and inflammation in the healing skin wound. Mol Cell Biol 22(15):5492-505. [PubMed: 12101242]  [MGI Ref ID J:100106]

Burk RF; Hill KE; Nakayama A; Mostert V; Levander XA; Motley AK; Johnson DA; Johnson JA; Freeman ML; Austin LM. 2008. Selenium deficiency activates mouse liver Nrf2-ARE but vitamin E deficiency does not. Free Radic Biol Med 44(8):1617-23. [PubMed: 18279678]  [MGI Ref ID J:134220]

Calkins MJ; Jakel RJ; Johnson DA; Chan K; Kan YW; Johnson JA. 2005. Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci U S A 102(1):244-9. [PubMed: 15611470]  [MGI Ref ID J:95887]

Chan JY; Kwong M. 2000. Impaired expression of glutathione synthetic enzyme genes in mice with targeted deletion of the Nrf2 basic-leucine zipper protein. Biochim Biophys Acta 1517(1):19-26. [PubMed: 11118612]  [MGI Ref ID J:66528]

Chan K; Kan YW. 1999. Nrf2 is essential for protection against acute pulmonary injury in mice. Proc Natl Acad Sci U S A 96(22):12731-6. [PubMed: 10535991]  [MGI Ref ID J:112943]

Chen PC; Vargas MR; Pani AK; Smeyne RJ; Johnson DA; Kan YW; Johnson JA. 2009. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte. Proc Natl Acad Sci U S A 106(8):2933-8. [PubMed: 19196989]  [MGI Ref ID J:146489]

Cheng X; Klaassen CD. 2008. Critical role of PPAR-alpha in perfluorooctanoic acid- and perfluorodecanoic acid-induced downregulation of Oatp uptake transporters in mouse livers. Toxicol Sci 106(1):37-45. [PubMed: 18703564]  [MGI Ref ID J:142114]

Davidson BA; Vethanayagam RR; Grimm MJ; Mullan BA; Raghavendran K; Blackwell TS; Freeman ML; Ayyasamy V; Singh KK; Sporn MB; Itagaki K; Hauser CJ; Knight PR; Segal BH. 2013. NADPH oxidase and nrf2 regulate gastric aspiration-induced inflammation and acute lung injury. J Immunol 190(4):1714-24. [PubMed: 23296708]  [MGI Ref ID J:193258]

Hagemann TL; Jobe EM; Messing A. 2012. Genetic ablation of Nrf2/antioxidant response pathway in Alexander disease mice reduces hippocampal gliosis but does not impact survival. PLoS One 7(5):e37304. [PubMed: 22693571]  [MGI Ref ID J:187423]

He X; Kan H; Cai L; Ma Q. 2009. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol 46(1):47-58. [PubMed: 19007787]  [MGI Ref ID J:149186]

Hoetzenecker W; Echtenacher B; Guenova E; Hoetzenecker K; Woelbing F; Bruck J; Teske A; Valtcheva N; Fuchs K; Kneilling M; Park JH; Kim KH; Kim KW; Hoffmann P; Krenn C; Hai T; Ghoreschi K; Biedermann T; Rocken M. 2012. ROS-induced ATF3 causes susceptibility to secondary infections during sepsis-associated immunosuppression. Nat Med 18(1):128-34. [PubMed: 22179317]  [MGI Ref ID J:180781]

Hu R; Xu C; Shen G; Jain MR; Khor TO; Gopalkrishnan A; Lin W; Reddy B; Chan JY; Kong AN. 2006. Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice. Cancer Lett 243(2):170-92. [PubMed: 16516379]  [MGI Ref ID J:114604]

Hu X; Roberts JR; Apopa PL; Kan YW; Ma Q. 2006. Accelerated ovarian failure induced by 4-vinyl cyclohexene diepoxide in Nrf2 null mice. Mol Cell Biol 26(3):940-54. [PubMed: 16428448]  [MGI Ref ID J:105555]

Hubbs AF; Benkovic SA; Miller DB; O'Callaghan JP; Battelli L; Schwegler-Berry D; Ma Q. 2007. Vacuolar leukoencephalopathy with widespread astrogliosis in mice lacking transcription factor nrf2. Am J Pathol 170(6):2068-76. [PubMed: 17525273]  [MGI Ref ID J:122195]

Jakel RJ; Townsend JA; Kraft AD; Johnson JA. 2007. Nrf2-mediated protection against 6-hydroxydopamine. Brain Res 1144:192-201. [PubMed: 17336276]  [MGI Ref ID J:121621]

Jiang T; Huang Z; Chan JY; Zhang DD. 2009. Nrf2 protects against As(III)-induced damage in mouse liver and bladder. Toxicol Appl Pharmacol 240(1):8-14. [PubMed: 19538980]  [MGI Ref ID J:153921]

Jiang T; Huang Z; Lin Y; Zhang Z; Fang D; Zhang DD. 2010. The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy. Diabetes 59(4):850-60. [PubMed: 20103708]  [MGI Ref ID J:164328]

Johnson DA; Amirahmadi S; Ward C; Fabry Z; Johnson JA. 2010. The absence of the pro-antioxidant transcription factor Nrf2 exacerbates experimental autoimmune encephalomyelitis. Toxicol Sci 114(2):237-46. [PubMed: 19910389]  [MGI Ref ID J:158285]

Kerns M; DePianto D; Yamamoto M; Coulombe PA. 2010. Differential modulation of keratin expression by sulforaphane occurs via Nrf2-dependent and -independent pathways in skin epithelia. Mol Biol Cell 21(23):4068-75. [PubMed: 20926689]  [MGI Ref ID J:182931]

Kim HJ; Nel AE. 2005. The role of phase II antioxidant enzymes in protecting memory T cells from spontaneous apoptosis in young and old mice. J Immunol 175(5):2948-59. [PubMed: 16116181]  [MGI Ref ID J:113246]

Kim KH; Sadikot RT; Xiao L; Christman JW; Freeman ML; Chan JY; Oh YK; Blackwell TS; Joo M. 2013. Nrf2 is essential for the expression of lipocalin-prostaglandin D synthase induced by prostaglandin D2. Free Radic Biol Med 65:1134-42. [PubMed: 24029383]  [MGI Ref ID J:205295]

Kraft AD; Lee JM; Johnson DA; Kan YW; Johnson JA. 2006. Neuronal sensitivity to kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element. J Neurochem 98(6):1852-65. [PubMed: 16945104]  [MGI Ref ID J:147263]

Lee JM; Calkins MJ; Chan K; Kan YW; Johnson JA. 2003. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 278(14):12029-38. [PubMed: 12556532]  [MGI Ref ID J:124820]

Lee JM; Chan K; Kan YW; Johnson JA. 2004. Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia. Proc Natl Acad Sci U S A 101(26):9751-6. [PubMed: 15210949]  [MGI Ref ID J:91407]

Lee JM; Shih AY; Murphy TH; Johnson JA. 2003. NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem 278(39):37948-56. [PubMed: 12842875]  [MGI Ref ID J:85659]

Leung L; Kwong M; Hou S; Lee C; Chan JY. 2003. Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. J Biol Chem 278(48):48021-9. [PubMed: 12968018]  [MGI Ref ID J:86725]

Li J; Stein TD; Johnson JA. 2004. Genetic dissection of systemic autoimmune disease in Nrf2-deficient mice. Physiol Genomics 18(3):261-72. [PubMed: 15173550]  [MGI Ref ID J:91823]

Lugade AA; Vethanayagam RR; Nasirikenari M; Bogner PN; Segal BH; Thanavala Y. 2011. Nrf2 regulates chronic lung inflammation and B-cell responses to nontypeable Haemophilus influenzae. Am J Respir Cell Mol Biol 45(3):557-65. [PubMed: 21216970]  [MGI Ref ID J:190224]

Ma Q; Battelli L; Hubbs AF. 2006. Multiorgan autoimmune inflammation, enhanced lymphoproliferation, and impaired homeostasis of reactive oxygen species in mice lacking the antioxidant-activated transcription factor Nrf2. Am J Pathol 168(6):1960-74. [PubMed: 16723711]  [MGI Ref ID J:109125]

McDonald JT; Kim K; Norris AJ; Vlashi E; Phillips TM; Lagadec C; Della Donna L; Ratikan J; Szelag H; Hlatky L; McBride WH. 2010. Ionizing radiation activates the Nrf2 antioxidant response. Cancer Res 70(21):8886-95. [PubMed: 20940400]  [MGI Ref ID J:165793]

Muramatsu H; Katsuoka F; Toide K; Shimizu Y; Furusako S; Yamamoto M. 2013. Nrf2 deficiency leads to behavioral, neurochemical and transcriptional changes in mice. Genes Cells 18(10):899-908. [PubMed: 23890231]  [MGI Ref ID J:214019]

Nakamura BN; Lawson G; Chan JY; Banuelos J; Cortes MM; Hoang YD; Ortiz L; Rau BA; Luderer U. 2010. Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age-dependent manner. Free Radic Biol Med 49(9):1368-79. [PubMed: 20692336]  [MGI Ref ID J:165602]

Pacchioni AM; Vallone J; Melendez RI; Shih A; Murphy TH; Kalivas PW. 2007. Nrf2 gene deletion fails to alter psychostimulant-induced behavior or neurotoxicity. Brain Res 1127(1):26-35. [PubMed: 17113054]  [MGI Ref ID J:116598]

Pi J; Leung L; Xue P; Wang W; Hou Y; Liu D; Yehuda-Shnaidman E; Lee C; Lau J; Kurtz TW; Chan JY. 2010. Deficiency in the nuclear factor E2-related factor-2 transcription factor results in impaired adipogenesis and protects against diet-induced obesity. J Biol Chem 285(12):9292-300. [PubMed: 20089859]  [MGI Ref ID J:161197]

Reisman SA; Csanaky IL; Aleksunes LM; Klaassen CD. 2009. Altered disposition of acetaminophen in Nrf2-null and Keap1-knockdown mice. Toxicol Sci 109(1):31-40. [PubMed: 19246624]  [MGI Ref ID J:149162]

Reisman SA; Csanaky IL; Yeager RL; Klaassen CD. 2009. Nrf2 activation enhances biliary excretion of sulfobromophthalein by inducing glutathione-S-transferase activity. Toxicol Sci 109(1):24-30. [PubMed: 19246623]  [MGI Ref ID J:149163]

Reisman SA; Yeager RL; Yamamoto M; Klaassen CD. 2009. Increased Nrf2 activation in livers from Keap1-knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species. Toxicol Sci 108(1):35-47. [PubMed: 19129213]  [MGI Ref ID J:146190]

Rockwell CE; Zhang M; Fields PE; Klaassen CD. 2012. Th2 skewing by activation of Nrf2 in CD4(+) T cells. J Immunol 188(4):1630-7. [PubMed: 22250088]  [MGI Ref ID J:181168]

Segal BH; Han W; Bushey JJ; Joo M; Bhatti Z; Feminella J; Dennis CG; Vethanayagam RR; Yull FE; Capitano M; Wallace PK; Minderman H; Christman JW; Sporn MB; Chan J; Vinh DC; Holland SM; Romani LR; Gaffen SL; Freeman ML; Blackwell TS. 2010. NADPH oxidase limits innate immune responses in the lungs in mice. PLoS One 5(3):e9631. [PubMed: 20300512]  [MGI Ref ID J:158908]

Shih AY; Imbeault S; Barakauskas V; Erb H; Jiang L; Li P; Murphy TH. 2005. Induction of the Nrf2-driven antioxidant response confers neuroprotection during mitochondrial stress in vivo. J Biol Chem 280(24):22925-36. [PubMed: 15840590]  [MGI Ref ID J:100270]

Tanaka Y; Aleksunes LM; Cui YJ; Klaassen CD. 2009. ANIT-induced intrahepatic cholestasis alters hepatobiliary transporter expression via Nrf2-dependent and independent signaling. Toxicol Sci 108(2):247-57. [PubMed: 19181614]  [MGI Ref ID J:147788]

Tsai JJ; Dudakov JA; Takahashi K; Shieh JH; Velardi E; Holland AM; Singer NV; West ML; Smith OM; Young LF; Shono Y; Ghosh A; Hanash AM; Tran HT; Moore MA; van den Brink MR. 2013. Nrf2 regulates haematopoietic stem cell function. Nat Cell Biol 15(3):309-16. [PubMed: 23434824]  [MGI Ref ID J:195199]

Vargas MR; Burton NC; Kutzke J; Gan L; Johnson DA; Schafer M; Werner S; Johnson JA. 2013. Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models. PLoS One 8(2):e56625. [PubMed: 23418589]  [MGI Ref ID J:199339]

Wang L; He X; Szklarz GD; Bi Y; Rojanasakul Y; Ma Q. 2013. The aryl hydrocarbon receptor interacts with nuclear factor erythroid 2-related factor 2 to mediate induction of NAD(P)H:quinoneoxidoreductase 1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Biochem Biophys 537(1):31-8. [PubMed: 23800876]  [MGI Ref ID J:206693]

Wruck CJ; Streetz K; Pavic G; Gotz ME; Tohidnezhad M; Brandenburg LO; Varoga D; Eickelberg O; Herdegen T; Trautwein C; Cha K; Kan YW; Pufe T. 2011. Nrf2 induces interleukin-6 (IL-6) expression via an antioxidant response element within the IL-6 promoter. J Biol Chem 286(6):4493-9. [PubMed: 21127061]  [MGI Ref ID J:169489]

Wu KC; Cui JY; Klaassen CD. 2011. Beneficial role of nrf2 in regulating NADPH generation and consumption. Toxicol Sci 123(2):590-600. [PubMed: 21775727]  [MGI Ref ID J:175825]

Wu KC; Cui JY; Klaassen CD. 2012. Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver. PLoS One 7(7):e39006. [PubMed: 22808024]  [MGI Ref ID J:189635]

Wu KC; Liu J; Klaassen CD. 2012. Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation. Toxicol Appl Pharmacol 262(3):321-9. [PubMed: 22627062]  [MGI Ref ID J:186170]

Wu KC; Liu JJ; Klaassen CD. 2012. Nrf2 activation prevents cadmium-induced acute liver injury. Toxicol Appl Pharmacol 263(1):14-20. [PubMed: 22677785]  [MGI Ref ID J:186162]

Xu C; Huang MT; Shen G; Yuan X; Lin W; Khor TO; Conney AH; Tony Kong AN. 2006. Inhibition of 7,12-Dimethylbenz(a)anthracene-Induced Skin Tumorigenesis in C57BL/6 Mice by Sulforaphane Is Mediated by Nuclear Factor E2-Related Factor 2. Cancer Res 66(16):8293-8296. [PubMed: 16912211]  [MGI Ref ID J:112179]

Xu W; Hellerbrand C; Kohler UA; Bugnon P; Kan YW; Werner S; Beyer TA. 2008. The Nrf2 transcription factor protects from toxin-induced liver injury and fibrosis. Lab Invest 88(10):1068-78. [PubMed: 18679376]  [MGI Ref ID J:140141]

Yeager RL; Reisman SA; Aleksunes LM; Klaassen CD. 2009. Introducing the 'TCDD-inducible AhR-Nrf2 gene battery'. Toxicol Sci 111(2):238-46. [PubMed: 19474220]  [MGI Ref ID J:154083]

Zhang L; Johnson D; Johnson JA. 2013. Deletion of Nrf2 impairs functional recovery, reduces clearance of myelin debris and decreases axonal remyelination after peripheral nerve injury. Neurobiol Dis 54:329-38. [PubMed: 23328769]  [MGI Ref ID J:197750]

Zhang YK; Wu KC; Klaassen CD. 2013. Genetic activation of Nrf2 protects against fasting-induced oxidative stress in livers of mice. PLoS One 8(3):e59122. [PubMed: 23527105]  [MGI Ref ID J:199381]

Zhang YK; Wu KC; Liu J; Klaassen CD. 2012. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. Toxicol Appl Pharmacol 264(3):305-14. [PubMed: 23017736]  [MGI Ref ID J:188996]

Zhao Z; Chen Y; Wang J; Sternberg P; Freeman ML; Grossniklaus HE; Cai J. 2011. Age-Related Retinopathy in NRF2-Deficient Mice. PLoS One 6(4):e19456. [PubMed: 21559389]  [MGI Ref ID J:172345]

Zheng H; Whitman SA; Wu W; Wondrak GT; Wong PK; Fang D; Zhang DD. 2011. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes 60(11):3055-66. [PubMed: 22025779]  [MGI Ref ID J:191402]

Zheng Y; Tao S; Lian F; Chau BT; Chen J; Sun G; Fang D; Lantz RC; Zhang DD. 2012. Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response. Toxicol Appl Pharmacol 265(3):292-9. [PubMed: 22975029]  [MGI Ref ID J:192867]

Zou Y; Hu M; Bao Q; Chan JY; Dai G. 2013. Nrf2 participates in regulating maternal hepatic adaptations to pregnancy. J Cell Sci 126(Pt 7):1618-25. [PubMed: 23418358]  [MGI Ref ID J:200452]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together. Our experience has been that homozygous breeders produced small litters and we recommend instead that either the male or female is a heterozygote.
Mating SystemHomozygote x Heterozygote         (Female x Male)   04-MAR-13
Heterozygote x Homozygote         (Female x Male)   04-MAR-13
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHeterozygous for Nfe2l2tm1Ywk  
$199.90Female or MaleHomozygous for Nfe2l2tm1Ywk  
Price per Pair (US dollars $)Pair Genotype
$399.80Heterozygous for Nfe2l2tm1Ywk x Homozygous for Nfe2l2tm1Ywk  
$399.80Homozygous for Nfe2l2tm1Ywk x Heterozygous for Nfe2l2tm1Ywk  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHeterozygous for Nfe2l2tm1Ywk  
$259.90Female or MaleHomozygous for Nfe2l2tm1Ywk  
Price per Pair (US dollars $)Pair Genotype
$519.80Heterozygous for Nfe2l2tm1Ywk x Homozygous for Nfe2l2tm1Ywk  
$519.80Homozygous for Nfe2l2tm1Ywk x Heterozygous for Nfe2l2tm1Ywk  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Heterozygote from the colony
   000664 C57BL/6J (approximate)
 
  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.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

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.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

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.

No Liability

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.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

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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