BRC No.RBRC01390
TypeTargeted MutationCartagena
SpeciesMus musculus
Strain nameB6.129P2-Nfe2l2<tm1Mym>/MymRbrc
Former Common nameNrf2 knockout mouse/C57BL6J
H-2 Haplotype
ES Cell lineE14 [129P2/OlaHsd]
Background strainC57BL/6
AppearanceBlack [a/a B/B C/C]
Strain developmentDeveloped by Masayuki Yamamoto, Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba in 1996. The targeting vector containing lacZ-neo cassette was transferred into E14 ES cells to replace the 1.2 kb segment containing the rest of the exon 5 coding sequence of the Nrf2 gene.
Strain descriptionNrf2 (Nfe2l2) Knockout mice. This strain is a useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs. A phenolic antioxidant significantly induced the expression of phase II enzymes such as glutathione S-transferase and NAD(P)H: quinone oxidoreductase in normal mice. However, in the homozygous Nrf2 deficient mice the induction of the phase II enzymes by a phenolic antioxidant was largely eliminated in the liver and intestine. Since Nrf2 is constantly degraded by proteasome under normal condition, it is hardly to detect Nrf2 protein in the absence of stimuli. Electrophilic chemicals, such as DEM (diethyl maleate) and tBHQ (tert-buthyl hydroquinone), are generally used to stabilize Nrf2. Or proteasomal inhibitors, such as MG132, are also effective increasing the protein amount of Nrf2. C57BL/6 background (RBRC01390), BALB/c background (RBRC02190), A/J background (RBRC02414), ICR mixed background (RBRC00984). Homozygous mutant mice are viable and fertile, but show lower reproductive performance.
Colony maintenanceHomozygote x Heterozygote [or Crossing to C57BL/6JJcl]
ReferencesBiochem. Biophys. Res. Commun., 236, 313-322, (1997) 9240432

Health Report

Examination Date / Room / Rack2021/01/05Room:3-6Rack:D


Gene info
Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter
Nfe2l2nuclear factor, erythroid derived 2, like 22Nfe2l2<tm1Mym>targeted mutation 1, Masayuki YamamotoNrf2

Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter
lacZbeta-galactosidase (E. coli)2

Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter
neoneomycin resistance gene (E. coli)2neo; neomycin;herpes simplex virus thymidine kinase promoter (HSV tk promoter)

Gene symbolGene nameChr.Allele symbolAllele nameCommon namesPromoter
nlsSV40 large T antigen nuclear localization signal (NLS)2nls


Donor DNASimian virus 40 Large T antigen nuclear localization signal (NLS), E. coli lacZ, herpes simplex virus thymidine kinase promoter (HSV tk promoter), E. coli neo, mouse Nrf2 genomic DNA
Research applicationFluorescent Proteins/lacZ System
Specific Term and ConditionsThe RECIPIENT of BIOLOGICAL RESOURCE shall obtain a prior written consent on use of it from the DEPOSITOR. In publishing the research results obtained by use of the BIOLOGICAL RESOURCE, a citation of the following literature(s) designated by the DEPOSITOR is requested. Biochem. Biophys. Res. Commun., 236, 313-322 (1997).The RECIPIENT agrees that it will acknowledge the DEPOSITOR as academically and scientifically appropriate in its articles when the Recipient publishes its data using these mice. Recipient should contact the DEPOSITOR in the case of application for any patents with the results from these mice.
DepositorMasayuki Yamamoto (University of Tsukuba)
Strain Statusan icon for Live miceLive mice
an icon for Frozen embryosFrozen embryos
an icon for Frozen spermFrozen sperm
Strain AvailabilityCryopreserved sperm (within 1 month)
Cryopreserved embryos (within 1 month)
Live mouse (1 to 3 months)
Additional Info.Mouse of the Month Oct 2005
Mouse of the Month Apr 2012
Genetic Background
Breeding characters
Genotyping protocol -PCR-
Approval form ( Japanese / English
Lab HP (Japanese)

BRC mice in Publications

Nakajima Y, Nakamura Y, Shigeeda W, Tomoyasu M, Deguchi H, Tanita T, Yamauchi K.
The Role of Tumor Necrosis Factor-alpha and Interferon-gamma in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells.
Allergol Int (2013) 23793505

Yao H, Sundar IK, Ahmad T, Lerner C, Gerloff J, Friedman AE, Phipps RP, Sime PJ, McBurney MW, Guarente L, Rahman I.
SIRT1 protects against cigarette smoke-induced lung oxidative stress via a FOXO3-dependent mechanism.
Am. J. Physiol. Lung Cell Mol. Physiol. 306(9) L816-28(2014) 24633890

Parada E, Egea J, Buendia I, Negredo P, Cunha AC, Cardoso S, Soares MP, Lopez MG.
The microglial alpha 7 acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing HO-1 via Nrf2.
Antioxid. Redox Signal. (2013) 23311871

Kay HY, Kim WD, Hwang SJ, Choi HS, Gilroy RK, Wan YJ, Kim SG.
Nrf2 inhibits LXRalpha-dependent hepatic lipogenesis by competing with FXR for acetylase binding.
Antioxid. Redox Signal. (2011) 21504366

Bae SH, Woo HA, Sung SH, Lee HE, Lee SK, Kil IS, Rhee SG.
Induction of sulfiredoxin via an Nrf2-dependent pathway and hyperoxidation of peroxiredoxin III in the lungs of mice exposed to hyperoxia.
Antioxid. Redox Signal. 11(5) 937-948(2009) 19086807

Zakkar M, Van der Heiden K, Luong le A, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, Haskard DO, Mason JC, Evans PC.
Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state.
Arterioscler. Thromb. Vasc. Biol. 29(11) 1851-7(2009) 19729611

Adenuga D, Caito S, Yao H, Sundar IK, Hwang JW, Chung S, Rahman I.
Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction.
Biochem. Biophys. Res. Commun. 403(3-4) 452-6(2010) 21094147

Chartoumpekis D, Ziros PG, Psyrogiannis A, Kyriazopoulou V, Papavassiliou AG, Habeos IG.
Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway.
Biochem. Biophys. Res. Commun. 396(2) 463-6(2010) 20417615

Marques L, Negre-Salvayre A, Costa L, Canonne-Hergaux F.
Iron gene expression profile in atherogenic Mox macrophages.
Biochim. Biophys. Acta (2016) 26972048

Dreger H, Westphal K, Wilck N, Baumann G, Stangl V, Stangl K, Meiners S.
Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2.
Cardiovasc. Res. 85(2) 395-403(2010) 19679681

Bae SH, Sung SH, Oh SY, Lim JM, Lee SK, Park YN, Lee HE, Kang D, Rhee SG.
Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage.
Cell Metab. 17(1) 73-84(2013) 23274085

Jeney V, Ramos S, Bergman ML, Bechmann I, Tischer J, Ferreira A, Oliveira-Marques V, Janse CJ, Rebelo S, Cardoso S, Soares MP.
Control of disease tolerance to malaria by nitric oxide and carbon monoxide.
Cell Rep 8(1) 126-36(2014) 24981859

Bancos S, Baglole CJ, Rahman I, Phipps RP.
Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Delta(12,14)-prostaglandin J(2) requires Nrf2.
Cell. Immunol. 262(1) 18-27(2010) 20064636

Chartoumpekis DV, Ziros PG, Psyrogiannis AI, Papavassiliou AG, Kyriazopoulou VE, Sykiotis GP, Habeos IG.
Nrf2 Represses FGF21 During Long-Term High-Fat Diet-Induced Obesity in Mice.
Diabetes (2011) 21852674

Bretscher P, Egger J, Shamshiev A, Trötzmüller M, Köfeler H, Carreira EM, Kopf M, Freigang S.
Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2.
EMBO Mol Med 7(5) 593-607(2015) 25770125

Freigang S, Ampenberger F, Spohn G, Heer S, Shamshiev AT, Kisielow J, Hersberger M, Yamamoto M, Bachmann MF, Kopf M.
Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis.
Eur. J. Immunol. (2011) 21484785

Sakai E, Morita M, Ohuchi M, Kido MA, Fukuma Y, Nishishita K, Okamoto K, Itoh K, Yamamoto M, Tsukuba T.
Effects of deficiency of Kelch-like ECH-associated protein 1 on skeletal organization: a mechanism for diminished nuclear factor of activated T cells cytoplasmic 1 during osteoclastogenesis.
FASEB J. 31(9) 4011-4022(2017) 28515152

Gruber F, Mayer H, Lengauer B, Mlitz V, Sanders JM, Kadl A, Bilban M, de Martin R, Wagner O, Kensler TW, Yamamoto M, Leitinger N, Tschachler E.
NF-E2-related factor 2 regulates the stress response to UVA-1-oxidized phospholipids in skin cells.
FASEB J. 24(1) 39-48(2010) 19720622

Kokubo T, Taniguchi Y, Kanayama M, Shimura M, Konishi Y, Kawagishi H, Yamamoto M, Shindo K and Yoshida A.
Extract of the mushroom Mycoleptodonoides aitchisonii induces a series of anti-oxidative and phase II detoxifying enzymes through activation of the transcription factor Nrf2.
Food Chemistry 129(1) 92-99(2011)

Su X, Li T, Liu Z, Huang Q, Liao K, Ren R, Lu L, Qi X, Wang M, Chen J, Zhou H, Leung EL, Pan H, Liu J, Wang H, Huang L, Liu L.
Licochalcone A activates Keap1-Nrf2 signaling to suppresses arthritis via phosphorylation of p62 at serine 349.
Free Radic. Biol. Med. (2017) 29233793

Athale J, Ulrich A, Chou Macgarvey N, Bartz RR, Welty-Wolf KE, Suliman HB, Piantadosi CA.
Nrf2 promotes alveolar mitochondrial biogenesis and resolution of lung injury in Staphylococcus aureus pneumonia in mice.
Free Radic. Biol. Med. 53(8) 1584-94(2012) 22940620

Abbas K, Breton J, Planson AG, Bouton C, Bignon J, Seguin C, Riquier S, Toledano MB, Drapier JC.
Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages.
Free Radic. Biol. Med. (2011) 21466852

Bae SH, Sung SH, Cho EJ, Lee SK, Lee HE, Woo HA, Yu DY, Kil IS, Rhee SG.
Concerted action of sulfiredoxin and peroxiredoxin I protects against alcohol-induced oxidative injury in mouse liver.
Hepatology 53(3) 945-53(2011) 21319188

Su Hyuk Ko, Da Jeong Rho, Jong Ik Jeon, Young-Jeon Kim, Hyun Ae Woo, Yun Kyung Lee and Jung Mogg Kim.
Bacteroides fragilis Enterotoxin Upregulates Heme Oxygenase-1 in Intestinal Epithelial Cells via a Mitogen-Activated Protein Kinases- and NF-κB-Dependent Pathway, Leading to Modulation of Apoptosis.
Infect. Immun. 84(7) (2016) 27324483

Lou Y, Guo Z, Zhu Y, Zhang G, Wang Y, Qi X, Lu L, Liu Z, Wu J.
Astragali radix and its main bioactive compounds activate the Nrf2-mediated signaling pathway to induce P-glycoprotein and breast cancer resistance protein.
J Ethnopharmacol 228 82-91(2018) 30243825

Qu C, Li B, Lai Y, Li H, Windust A, Hofseth LJ, Nagarkatti M, Nagarkatti P, Wang XL, Tang D, Janicki JS, Tian X, Cui T.
Identifying panaxynol, a natural activator of nuclear factor erythroid-2 related factor 2 (Nrf2) from American ginseng as a suppressor of inflamed macrophage-induced cardiomyocyte hypertrophy.
J Ethnopharmacol 168 326-36(2015) 25882312

Yeang HX, Hamdam JM, Al-Huseini LM, Sethu S, Djouhri L, Walsh J, Kitteringham N, Park BK, Goldring CE, Sathish JG.
Loss of Transcription Factor Nuclear Factor-Erythroid 2 (NF-E2) p45-related Factor-2 (Nrf2) Leads to Dysregulation of Immune Functions, Redox Homeostasis, and Intracellular Signaling in Dendritic Cells.
J. Biol. Chem. 287(13) 10556-64(2012) 22311972

Kim H, Jung Y, Shin BS, Kim H, Song H, Bae SH, Rhee SG, Jeong W.
Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2.
J. Biol. Chem. 285(45) 34419-28(2010) 20826812

Takemoto Y, Inaba S, Zhang L, Tsujikawa K, Uezumi A, Fukada SI.
Implication of basal lamina dependency in survival of Nrf2-null muscle stem cells via an antioxidative-independent mechanism.
J. Cell. Physiol. (2018) 30070693

Paiva CN, Feij DF, Dutra FF, Carneiro VC, Freitas GB, Alves LS, Mesquita J, Fortes GB, Figueiredo RT, Souza HS, Fantappi MR, Lannes-Vieira J, Bozza MT.
Oxidative stress fuels Trypanosoma cruzi infection in mice.
J. Clin. Invest. 122(7) 2531-42(2012) 22728935

Gatbonton-Schwager TN, Letterio JJ, Tochtrop GP.
Bryonolic Acid Transcriptional Control of Anti-inflammatory and Antioxidant Genes in Macrophages in Vitro and in Vivo.
J. Nat. Prod. (2012) 22339499

Ashino T, Yamanaka R, Yamamoto M, Shimokawa H, Sekikawa K, Iwakura Y, Shioda S, Numazawa S, Yoshida T.
Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages.
Mol. Immunol. 45(7) 2106-15(2008) 18022235

Jo C, Gundemir S, Pritchard S, Jin YN, Rahman I, Johnson GV.
Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52.
Nat Commun 5 3496(2014) 24667209

Maoping Tang, Changyi Ji, Susanne Pallo, Irfan Rahman, Gail V.W. Johnson.
Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age dependent manner.
Neurobiol. Aging (2018) 29304346

Mendez-David I, Tritschler L, Ali ZE, Damiens MH, Pallardy M, David DJ, Kerdine-Röer S, Gardier AM.
Nrf2-signaling and BDNF: A new target for the antidepressant-like activity of chronic fluoxetine treatment in a mouse model of anxiety/depression.
Neurosci. Lett. (2015) 25916883

Takayama K, Kaneko H, Kataoka K, Kimoto R, Hwang SJ, Ye F, Nagasaka Y, Tsunekawa T, Matsuura T, Nonobe N, Ito Y, Terasaki H.
Nuclear Factor (Erythroid-Derived)-Related Factor 2-Associated Retinal Pigment Epithelial Cell Protection under Blue Light-Induced Oxidative Stress.
Oxid Med Cell Longev (2016) 27774118

Benson SA, Ernst JD.
TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms.
PLoS ONE 4(7) e6329(2009) 19629181

Suzuki R, Nakamura Y, Chiba S, Mizuno T, Abe K, Horii Y, Nagashima H, Tanita T, Yamauchi K.
Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin.
Pulm Pharmacol Ther (2016) 27179426

Santarino IB, Viegas MS, Domingues NS, Ribeiro AM, Soares MP, Vieira OV.
Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis.
Sci Rep 7(1) 5812(2017) 28724916

El Ali Z, Gerbeix C, Hemon P, Esser PR, Martin SF, Pallardy M, Kerdine-R mer S.
Allergic Skin Inflammation Induced by Chemical Sensitizers Is Controlled by the Transcription Factor Nrf2.
Toxicol. Sci. (2013) 23564646